/**
* Note: This file may contain artifacts of previous malicious infection.
* However, the dangerous code has been removed, and the file is now safe to use.
*/

/**
 * @file
 * Pathologic text filter for Drupal.
 *
 * This input filter attempts to make sure that link and image paths will
 * always be correct, even when domain names change, content is moved from one
 * server to another, the Clean URLs feature is toggled, etc.
 */

/**
 * Implements hook_filter_info().
 */
function pathologic_filter_info() {
  return array(
    'pathologic' => array(
      'title' => t('Correct URLs with Pathologic'),
      'process callback' => '_pathologic_filter',
      'settings callback' => '_pathologic_settings',
      'default settings' => array(
        'local_paths' => '',
        'protocol_style' => 'full',
      ),
      // Set weight to 50 so that it will hopefully appear at the bottom of
      // filter lists by default. 50 is the maximum value of the weight menu
      // for each row in the filter table (the menu is hidden by JavaScript to
      // use table row dragging instead when JS is enabled).
      'weight' => 50,
    )
  );
}

/**
 * Settings callback for Pathologic.
 */
function _pathologic_settings($form, &$form_state, $filter, $format, $defaults, $filters) {
  return array(
    'reminder' => array(
      '#type' => 'item',
      '#title' => t('In most cases, Pathologic should be the <em>last</em> filter in the &ldquo;Filter processing order&rdquo; list.'),
      '#weight' => -10,
    ),
    'protocol_style' => array(
      '#type' => 'radios',
      '#title' => t('Processed URL format'),
      '#default_value' => isset($filter->settings['protocol_style']) ? $filter->settings['protocol_style'] : $defaults['protocol_style'],
      '#options' => array(
        'full' => t('Full URL (<code>http://example.com/foo/bar</code>)'),
        'proto-rel' => t('Protocol relative URL (<code>//example.com/foo/bar</code>)'),
        'path' => t('Path relative to server root (<code>/foo/bar</code>)'),
      ),
      '#description' => t('The <em>Full URL</em> option is best for stopping broken images and links in syndicated content (such as in RSS feeds), but will likely lead to problems if your site is accessible by both HTTP and HTTPS. Paths output with the <em>Protocol relative URL</em> option will avoid such problems, but feed readers and other software not using up-to-date standards may be confused by the paths. The <em>Path relative to server root</em> option will avoid problems with sites accessible by both HTTP and HTTPS with no compatibility concerns, but will absolutely not fix broken images and links in syndicated content.'),
      '#weight' => 10,
    ),
    'local_paths' => array(
      '#type' => 'textarea',
      '#title' =>  t('All base paths for this site'),
      '#default_value' => isset($filter->settings['local_paths']) ? $filter->settings['local_paths'] : $defaults['local_paths'],
        '#description' => t('If this site is or was available at more than one base path or URL, enter them here, separated by line breaks. For example, if this site is live at <code>http://example.com/</code> but has a staging version at <code>http://dev.example.org/staging/</code>, you would enter both those URLs here. If confused, please read <a href="!docs">Pathologic&rsquo;s documentation</a> for more information about this option and what it affects.', array('!docs' => 'http://drupal.org/node/257026')),
      '#weight' => 20,
    ),
  );
}

/**
 * Pathologic filter callback.
 *
 * Previous versions of this module worked (or, rather, failed) under the
 * assumption that $langcode contained the language code of the node. Sadly,
 * this isn't the case.
 * @see http://drupal.org/node/1812264
 * However, it turns out that the language of the current node isn't as
 * important as the language of the node we're linking to, and even then only
 * if language path prefixing (eg /ja/node/123) is in use. REMEMBER THIS IN THE
 * FUTURE, ALBRIGHT.
 *
 * The below code uses the @ operator before parse_url() calls because in PHP
 * 5.3.2 and earlier, parse_url() causes a warning of parsing fails. The @
 * operator is usually a pretty strong indicator of code smell, but please don't
 * judge me by it in this case; ordinarily, I despise its use, but I can't find
 * a cleaner way to avoid this problem (using set_error_handler() could work,
 * but I wouldn't call that "cleaner"). Fortunately, Drupal 8 will require at
 * least PHP 5.3.5, so this mess doesn't have to spread into the D8 branch of
 * Pathologic.
 * @see https://drupal.org/node/2104849
 *
 * @todo Can we do the parsing of the local path settings somehow when the
 * settings form is submitted instead of doing it here?
 */
function _pathologic_filter($text, $filter, $format, $langcode, $cache, $cache_id) {
  // Get the base URL and explode it into component parts. We add these parts
  // to the exploded local paths settings later.
  global $base_url;
  $base_url_parts = @parse_url($base_url . '/');
  // Since we have to do some gnarly processing even before we do the *really*
  // gnarly processing, let's static save the settings - it'll speed things up
  // if, for example, we're importing many nodes, and not slow things down too
  // much if it's just a one-off. But since different input formats will have
  // different settings, we build an array of settings, keyed by format ID.
  $cached_settings = &drupal_static(__FUNCTION__, array());
  if (!isset($cached_settings[$filter->format])) {
    $filter->settings['local_paths_exploded'] = array();
    if ($filter->settings['local_paths'] !== '') {
      // Build an array of the exploded local paths for this format's settings.
      // array_filter() below is filtering out items from the array which equal
      // FALSE - so empty strings (which were causing problems.
      // @see http://drupal.org/node/1727492
      $local_paths = array_filter(array_map('trim', explode("\n", $filter->settings['local_paths'])));
      foreach ($local_paths as $local) {
        $parts = @parse_url($local);
        // Okay, what the hellish "if" statement is doing below is checking to
        // make sure we aren't about to add a path to our array of exploded
        // local paths which matches the current "local" path. We consider it
        // not a match, if…
        // @todo: This is pretty horrible. Can this be simplified?
        if (
          (
            // If this URI has a host, and…
            isset($parts['host']) &&
            (
              // Either the host is different from the current host…
              $parts['host'] !== $base_url_parts['host']
              // Or, if the hosts are the same, but the paths are different…
              // @see http://drupal.org/node/1875406
              || (
                // Noobs (like me): "xor" means "true if one or the other are
                // true, but not both."
                (isset($parts['path']) xor isset($base_url_parts['path']))
                || (isset($parts['path']) && isset($base_url_parts['path']) && $parts['path']  !== $base_url_parts['path'])
              )
            )
          ) ||
          // Or…
          (
            // The URI doesn't have a host…
            !isset($parts['host'])
          ) &&
          // And the path parts don't match (if either doesn't have a path
          // part, they can't match)…
          (
            !isset($parts['path']) ||
            !isset($base_url_parts['path']) ||
            $parts['path'] !== $base_url_parts['path']
          )
        ) {
          // Add it to the list.
          $filter->settings['local_paths_exploded'][] = $parts;
        }
      }
    }
    // Now add local paths based on "this" server URL.
    $filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path']);
    $filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path'], 'host' => $base_url_parts['host']);
    // We'll also just store the host part separately for easy access.
    $filter->settings['base_url_host'] = $base_url_parts['host'];

    $cached_settings[$filter->format] = $filter->settings;
  }
  // Get the language code for the text we're about to process.
  $cached_settings['langcode'] = $langcode;
  // And also take note of which settings in the settings array should apply.
  $cached_settings['current_settings'] = &$cached_settings[$filter->format];

  // Now that we have all of our settings prepared, attempt to process all
  // paths in href, src, action or longdesc HTML attributes. The pattern below
  // is not perfect, but the callback will do more checking to make sure the
  // paths it receives make sense to operate upon, and just return the original
  // paths if not.
  return preg_replace_callback('~ (href|src|action|longdesc)="([^"]+)~i', '_pathologic_replace', $text);
}

/**
 * Process and replace paths. preg_replace_callback() callback.
 */
function _pathologic_replace($matches) {
  // Get the base path.
  global $base_path;

  // Get the settings for the filter. Since we can't pass extra parameters
  // through to a callback called by preg_replace_callback(), there's basically
  // three ways to do this that I can determine: use eval() and friends; abuse
  // globals; or abuse drupal_static(). The latter is the least offensive, I
  // guess… Note that we don't do the & thing here so that we can modify
  // $cached_settings later and not have the changes be "permanent."
  $cached_settings = drupal_static('_pathologic_filter');
  // If it appears the path is a scheme-less URL, prepend a scheme to it.
  // parse_url() cannot properly parse scheme-less URLs. Don't worry; if it
  // looks like Pathologic can't handle the URL, it will return the scheme-less
  // original.
  // @see https://drupal.org/node/1617944
  // @see https://drupal.org/node/2030789
  if (strpos($matches[2], '//') === 0) {
    if (isset($_SERVER['https']) && strtolower($_SERVER['https']) === 'on') {
      $matches[2] = 'https:' . $matches[2];
    }
    else {
      $matches[2] = 'http:' . $matches[2];
    }
  }
  // Now parse the URL after reverting HTML character encoding.
  // @see http://drupal.org/node/1672932
  $original_url = htmlspecialchars_decode($matches[2]);
  // …and parse the URL
  $parts = @parse_url($original_url);
  // Do some more early tests to see if we should just give up now.
  if (
    // If parse_url() failed, give up.
    $parts === FALSE
    || (
      // If there's a scheme part and it doesn't look useful, bail out.
      isset($parts['scheme'])
      // We allow for the storage of permitted schemes in a variable, though we
      // don't actually give the user any way to edit it at this point. This
      // allows developers to set this array if they have unusual needs where
      // they don't want Pathologic to trip over a URL with an unusual scheme.
      // @see http://drupal.org/node/1834308
      // "files" and "internal" are for Path Filter compatibility.
      && !in_array($parts['scheme'], variable_get('pathologic_scheme_whitelist', array('http', 'https', 'files', 'internal')))
    )
    // Bail out if it looks like there's only a fragment part.
    || (isset($parts['fragment']) && count($parts) === 1)
  ) {
    // Give up by "replacing" the original with the same.
    return $matches[0];
  }

  if (isset($parts['path'])) {
    // Undo possible URL encoding in the path.
    // @see http://drupal.org/node/1672932
    $parts['path'] = rawurldecode($parts['path']);
  }
  else {
    $parts['path'] = '';
  }

  // Check to see if we're dealing with a file.
  // @todo Should we still try to do path correction on these files too?
  if (isset($parts['scheme']) && $parts['scheme'] === 'files') {
    // Path Filter "files:" support. What we're basically going to do here is
    // rebuild $parts from the full URL of the file.
    $new_parts = @parse_url(file_create_url(file_default_scheme() . '://' . $parts['path']));
    // If there were query parts from the original parsing, copy them over.
    if (!empty($parts['query'])) {
      $new_parts['query'] = $parts['query'];
    }
    $new_parts['path'] = rawurldecode($new_parts['path']);
    $parts = $new_parts;
    // Don't do language handling for file paths.
    $cached_settings['is_file'] = TRUE;
  }
  else {
    $cached_settings['is_file'] = FALSE;
  }

  // Let's also bail out of this doesn't look like a local path.
  $found = FALSE;
  // Cycle through local paths and find one with a host and a path that matches;
  // or just a host if that's all we have; or just a starting path if that's
  // what we have.
  foreach ($cached_settings['current_settings']['local_paths_exploded'] as $exploded) {
    // If a path is available in both…
    if (isset($exploded['path']) && isset($parts['path'])
      // And the paths match…
      && strpos($parts['path'], $exploded['path']) === 0
      // And either they have the same host, or both have no host…
      && (
        (isset($exploded['host']) && isset($parts['host']) && $exploded['host'] === $parts['host'])
        || (!isset($exploded['host']) && !isset($parts['host']))
      )
    ) {
      // Remove the shared path from the path. This is because the "Also local"
      // path was something like http://foo/bar and this URL is something like
      // http://foo/bar/baz; or the "Also local" was something like /bar and
      // this URL is something like /bar/baz. And we only care about the /baz
      // part.
      $parts['path'] = drupal_substr($parts['path'], drupal_strlen($exploded['path']));
      $found = TRUE;
      // Break out of the foreach loop
      break;
    }
    // Okay, we didn't match on path alone, or host and path together. Can we
    // match on just host? Note that for this one we are looking for paths which
    // are just hosts; not hosts with paths.
    elseif ((isset($parts['host']) && !isset($exploded['path']) && isset($exploded['host']) && $exploded['host'] === $parts['host'])) {
      // No further editing; just continue
      $found = TRUE;
      // Break out of foreach loop
      break;
    }
    // Is this is a root-relative url (no host) that didn't match above?
    // Allow a match if local path has no path,
    // but don't "break" because we'd prefer to keep checking for a local url
    // that might more fully match the beginning of our url's path
    // e.g.: if our url is /foo/bar we'll mark this as a match for
    // http://example.com but want to keep searching and would prefer a match
    // to http://example.com/foo if that's configured as a local path
    elseif (!isset($parts['host']) && (!isset($exploded['path']) || $exploded['path'] === $base_path)) {
      $found = TRUE;
    }
  }

  // If the path is not within the drupal root return original url, unchanged
  if (!$found) {
    return $matches[0];
  }

  // Okay, format the URL.
  // If there's still a slash lingering at the start of the path, chop it off.
  $parts['path'] = ltrim($parts['path'],'/');

  // Examine the query part of the URL. Break it up and look through it; if it
  // has a value for "q", we want to use that as our trimmed path, and remove it
  // from the array. If any of its values are empty strings (that will be the
  // case for "bar" if a string like "foo=3&bar&baz=4" is passed through
  // parse_str()), replace them with NULL so that url() (or, more
  // specifically, drupal_http_build_query()) can still handle it.
  if (isset($parts['query'])) {
    parse_str($parts['query'], $parts['qparts']);
    foreach ($parts['qparts'] as $key => $value) {
      if ($value === '') {
        $parts['qparts'][$key] = NULL;
      }
      elseif ($key === 'q') {
        $parts['path'] = $value;
        unset($parts['qparts']['q']);
      }
    }
  }
  else {
    $parts['qparts'] = NULL;
  }

  // If we don't have a path yet, bail out.
  if (!isset($parts['path'])) {
    return $matches[0];
  }

  // If we didn't previously identify this as a file, check to see if the file
  // exists now that we have the correct path relative to DRUPAL_ROOT
  if (!$cached_settings['is_file']) {
    $cached_settings['is_file'] = !empty($parts['path']) && is_file(DRUPAL_ROOT . '/'. $parts['path']);
  }

  // Okay, deal with language stuff.
  if ($cached_settings['is_file']) {
    // If we're linking to a file, use a fake LANGUAGE_NONE language object.
    // Otherwise, the path may get prefixed with the "current" language prefix
    // (eg, /ja/misc/message-24-ok.png)
    $parts['language_obj'] = (object) array('language' => LANGUAGE_NONE, 'prefix' => '');
  }
  else {
    // Let's see if we can split off a language prefix from the path.
    if (module_exists('locale')) {
      // Sometimes this file will be require_once-d by the locale module before
      // this point, and sometimes not. We require_once it ourselves to be sure.
      require_once DRUPAL_ROOT . '/includes/language.inc';
      list($language_obj, $path) = language_url_split_prefix($parts['path'], language_list());
      if ($language_obj) {
        $parts['path'] = $path;
        $parts['language_obj'] = $language_obj;
      }
    }
  }

  // If we get to this point and $parts['path'] is now an empty string (which
  // will be the case if the path was originally just "/"), then we
  // want to link to <front>.
  if ($parts['path'] === '') {
    $parts['path'] = '<front>';
  }
  // Build the parameters we will send to url()
  $url_params = array(
    'path' => $parts['path'],
    'options' => array(
      'query' => $parts['qparts'],
      'fragment' => isset($parts['fragment']) ? $parts['fragment'] : NULL,
      // Create an absolute URL if protocol_style is 'full' or 'proto-rel', but
      // not if it's 'path'.
      'absolute' => $cached_settings['current_settings']['protocol_style'] !== 'path',
      // If we seem to have found a language for the path, pass it along to
      // url(). Otherwise, ignore the 'language' parameter.
      'language' => isset($parts['language_obj']) ? $parts['language_obj'] : NULL,
      // A special parameter not actually used by url(), but we use it to see if
      // an alter hook implementation wants us to just pass through the original
      // URL.
      'use_original' => FALSE,
    ),
  );

  // Add the original URL to the parts array
  $parts['original'] = $original_url;

  // Now alter!
  // @see http://drupal.org/node/1762022
  drupal_alter('pathologic', $url_params, $parts, $cached_settings);

  // If any of the alter hooks asked us to just pass along the original URL,
  // then do so.
  if ($url_params['options']['use_original']) {
    return $matches[0];
  }

  // If the path is for a file and clean URLs are disabled, then the path that
  // url() will create will have a q= query fragment, which won't work for
  // files. To avoid that, we use this trick to temporarily turn clean URLs on.
  // This is horrible, but it seems to be the sanest way to do this.
  // @see http://drupal.org/node/1672430
  // @todo Submit core patch allowing clean URLs to be toggled by option sent
  // to url()?
  if (!empty($cached_settings['is_file'])) {
    $cached_settings['orig_clean_url'] = !empty($GLOBALS['conf']['clean_url']);
    if (!$cached_settings['orig_clean_url']) {
      $GLOBALS['conf']['clean_url'] = TRUE;
    }
  }

  // Now for the url() call. Drumroll, please…
  $url = url($url_params['path'], $url_params['options']);

  // If we turned clean URLs on before to create a path to a file, turn them
  // back off.
  if ($cached_settings['is_file'] && !$cached_settings['orig_clean_url']) {
    $GLOBALS['conf']['clean_url'] = FALSE;
  }

  // If we need to create a protocol-relative URL, then convert the absolute
  // URL we have now.
  if ($cached_settings['current_settings']['protocol_style'] === 'proto-rel') {
    // Now, what might have happened here is that url() returned a URL which
    // isn't on "this" server due to a hook_url_outbound_alter() implementation.
    // We don't want to convert the URL in that case. So what we're going to
    // do is cycle through the local paths again and see if the host part of
    // $url matches with the host of one of those, and only alter in that case.
    $url_parts = @parse_url($url);
    if (!empty($url_parts['host']) && $url_parts['host'] === $cached_settings['current_settings']['base_url_host']) {
      $url = _pathologic_url_to_protocol_relative($url);
    }
  }

  // Apply HTML character encoding, as is required for HTML attributes.
  // @see http://drupal.org/node/1672932
  $url = check_plain($url);
  // $matches[1] will be the tag attribute; src, href, etc.
  return " {$matches[1]}=\"{$url}";
}

/**
 * Convert a full URL with a protocol to a protocol-relative URL.
 *
 * As the Drupal core url() function doesn't support protocol-relative URLs, we
 * work around it by just creating a full URL and then running it through this
 * to strip off the protocol.
 *
 * Though this is just a one-liner, it's placed in its own function so that it
 * can be called independently from our test code.
 */
function _pathologic_url_to_protocol_relative($url) {
  return preg_replace('~^https?://~', '//', $url);
}
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						<ul class="links inline"><li  class="first menu-251 depth-1"><div class="menu-item-wrapper"><a href="/">Home</a></div></li><li  class="has-children menu-2052 depth-1 active-ancestor" title="What are stem cells? Learn about their abilities and how they build and repair the body. Includes ethics, web links and a glossary with scientific words used in stem cell research."><div class="menu-item-wrapper"><a href="/stem-cells-and-regenerative-medicine" title="What are stem cells? Learn about their abilities and how they build and repair the body. Includes ethics, web links and a glossary with scientific words used in stem cell research.">About stem cells</a><ul><li  class="first has-children menu-1957 depth-2 active-ancestor" title="More about diseases researchers and clinicians at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh, study. Diseases include brain cancer, diabetes, leukaemia, liver disease, motor neurone disease, multiple sclerosis and parkinson’s disease."><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study" title="More about diseases researchers and clinicians at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh, study. Diseases include brain cancer, diabetes, leukaemia, liver disease, motor neurone disease, multiple sclerosis and parkinson’s disease.">Diseases we study</a><ul><li  class="first menu-2321 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/information-patients">Information for patients</a></div></li><li  class="menu-2538 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/brain-cancer">Brain cancer</a></div></li><li  class="menu-3570 depth-3" title="Macrophage cell therapy for liver cirrhosis"><div class="menu-item-wrapper"><a href="/macrophage-cell-therapy-liver-cirrhosis" title="Macrophage cell therapy for liver cirrhosis">Cell Therapy Trials</a></div></li><li  class="menu-3279 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/heart-disease">Heart disease</a></div></li><li  class="menu-2540 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/leukaemia">Leukaemia</a></div></li><li  class="menu-2541 depth-3 active"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/liver-disease-and-cancer" class="active">Liver disease and cancer</a></div></li><li  class="menu-2542 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/motor-neurone-disease">Motor neurone disease</a></div></li><li  class="menu-2537 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/multiple-sclerosis">Multiple sclerosis</a></div></li><li  class="last menu-2543 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/parkinsons-disease">Parkinson&#039;s disease</a></div></li></ul></div></li><li  class="menu-2056 depth-2" title="What are stem cells? Find out more about stem cells, their abilities and how they build and repair the body."><div class="menu-item-wrapper"><a href="/about-stem-cells/what-are-stem-cells" title="What are stem cells? Find out more about stem cells, their abilities and how they build and repair the body.">What are stem cells?</a></div></li><li  class="menu-2271 depth-2" title="Ethics: learn about some of the ethical issues surrounding stem cell research and regenerative medicine."><div class="menu-item-wrapper"><a href="/about-stem-cells/ethics" title="Ethics: learn about some of the ethical issues surrounding stem cell research and regenerative medicine.">Ethics</a></div></li><li  class="menu-2270 depth-2"><div class="menu-item-wrapper"><a href="/about-stem-cells/history">History</a></div></li><li  class="menu-2272 depth-2" title="Web links: useful information on stem cells and regenerative medicine."><div class="menu-item-wrapper"><a href="/about-stem-cells/web-links" title="Web links: useful information on stem cells and regenerative medicine.">Web links</a></div></li><li  class="menu-2273 depth-2" title="Glossary: look up definitions of scientific words often used in stem cell research and regenerative medicine."><div class="menu-item-wrapper"><a href="/about-stem-cells/glossary" title="Glossary: look up definitions of scientific words often used in stem cell research and regenerative medicine.">Glossary</a></div></li><li  class="last menu-2320 depth-2"><div class="menu-item-wrapper"><a href="/about-stem-cells/public-engagement">Public engagement</a></div></li></ul></div></li><li  class="has-children menu-1955 depth-1"><div class="menu-item-wrapper"><a href="/research">Research</a><ul><li  class="first has-children menu-1943 depth-2" title="More about research groups and principal investigators at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/research/research-groups" title="More about research groups and principal investigators at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">Research groups</a><ul><li  class="first menu-2869 depth-3"><div class="menu-item-wrapper"><a href="/research/group/chromatin-structure-and-cellular-identity">Abdenour Soufi</a></div></li><li  class="menu-1958 depth-3"><div class="menu-item-wrapper"><a href="/research/group/ontogeny-haematopoietic-stem-cells">Alexander Medvinsky</a></div></li><li  class="menu-2040 depth-3"><div class="menu-item-wrapper"><a href="/research/group/stem-cell-genome-engineering">Andrew Smith</a></div></li><li  class="menu-2041 depth-3"><div class="menu-item-wrapper"><a href="/research/group/remyelination-multiple-sclerosis">Anna Williams</a></div></li><li  class="menu-2042 depth-3"><div class="menu-item-wrapper"><a href="/research/group/adult-tissue-cell-plasticity-reprogramming-fate-change-and-regeneration">Anura Rambukkana</a></div></li><li  class="menu-2043 depth-3"><div class="menu-item-wrapper"><a href="/research/group/tissue-development-regeneration-and-repair">Bruno Péault</a></div></li><li  class="menu-2044 depth-3"><div class="menu-item-wrapper"><a href="/research/group/myelination-and-repair-cns">Charles ffrench-Constant</a></div></li><li  class="menu-2045 depth-3"><div class="menu-item-wrapper"><a href="/research/group/thymus-generation-and-regeneration">Clare Blackburn</a></div></li><li  class="menu-2343 depth-3"><div class="menu-item-wrapper"><a href="/research/group/liver-tissue-development-and-engineering">Dave Hay</a></div></li><li  class="menu-2836 depth-3" title="Prof Donal O&#039;Carroll&#039;s group at the MRC Centre for Regenerative Medicine, University of Edinburgh, works on RNA function in germ and stem cell biology."><div class="menu-item-wrapper"><a href="/research/group/rna-function-germ-and-stem-cell-biology" title="Prof Donal O&#039;Carroll&#039;s group at the MRC Centre for Regenerative Medicine, University of Edinburgh, works on RNA function in germ and stem cell biology.">Donal O&#039;Carroll</a></div></li><li  class="menu-3355 depth-3" title="Mechanisms of regeneration with age"><div class="menu-item-wrapper"><a href="/research/group/manipulating-stem-cell-niche-promote-regeneration" title="Mechanisms of regeneration with age">Elaine Emmerson</a></div></li><li  class="menu-3569 depth-3" title="Quantitative Biology of Pattern Formation"><div class="menu-item-wrapper"><a href="/research/group/quantitative-biology-pattern-formation" title="Quantitative Biology of Pattern Formation">Guillaume Blin</a></div></li><li  class="menu-1973 depth-3"><div class="menu-item-wrapper"><a href="/research/group/embryonic-stem-cell-biology">Ian Chambers</a></div></li><li  class="menu-2345 depth-3"><div class="menu-item-wrapper"><a href="/research/group/redirecting-cell-fate">Ian Wilmut</a></div></li><li  class="menu-2870 depth-3"><div class="menu-item-wrapper"><a href="/research/group/developmental-origins-blood-stem-cells-and-leukaemia">Katrin Ottersbach</a></div></li><li  class="menu-2347 depth-3"><div class="menu-item-wrapper"><a href="/research/group/biology-reprogramming">Keisuke Kaji</a></div></li><li  class="menu-2348 depth-3"><div class="menu-item-wrapper"><a href="/research/group/mesoderm-and-haematopoietic-differentiation">Lesley Forrester</a></div></li><li  class="menu-3465 depth-3" title="Computational biology of cell populations"><div class="menu-item-wrapper"><a href="/research/group/computational-biology-cell-populations" title="Computational biology of cell populations">Linus Schumacher</a></div></li><li  class="menu-3566 depth-3" title="Cell and tissue monitoring"><div class="menu-item-wrapper"><a href="/research/group/cell-and-tissue-monitoring" title="Cell and tissue monitoring">Pierre Bagnaninchi</a></div></li><li  class="menu-3567 depth-3" title="Epigenetics and Brain Development"><div class="menu-item-wrapper"><a href="/research/group/epigenetics-and-brain-development" title="Epigenetics and Brain Development">Robert Illingworth</a></div></li><li  class="menu-2349 depth-3"><div class="menu-item-wrapper"><a href="/research/group/pluripotent-stem-cell-differentiation">Sally Lowell</a></div></li><li  class="menu-2351 depth-3"><div class="menu-item-wrapper"><a href="/research/group/stem-cell-bioinformatics">Simon Tomlinson</a></div></li><li  class="menu-2352 depth-3"><div class="menu-item-wrapper"><a href="/research/group/neural-stem-cells-and-brain-cancer">Steve Pollard</a></div></li><li  class="menu-2353 depth-3"><div class="menu-item-wrapper"><a href="/research/group/liver-stem-cells-and-regeneration">Stuart Forbes</a></div></li><li  class="menu-2354 depth-3"><div class="menu-item-wrapper"><a href="/research/group/mechanisms-neurodegeneration">Tilo Kunath</a></div></li><li  class="last menu-2355 depth-3"><div class="menu-item-wrapper"><a href="/research/group/early-embryo-development">Val Wilson</a></div></li></ul></div></li><li  class="menu-3296 depth-2"><div class="menu-item-wrapper"><a href="/research/research-themes">Research themes</a></div></li><li  class="menu-1941 depth-2"><div 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href="/research/associate/vascular-regeneration-endothelial-progenitor-cells">Mairi Brittan</a></div></li><li  class="menu-2378 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/integrated-chemical-biophysics">Manfred Auer</a></div></li><li  class="menu-2369 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/snbts-cellular-therapy-development-centre">Marc Turner</a></div></li><li  class="menu-3308 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/enzyme-deregulation-disease">Maria Christophorou</a></div></li><li  class="menu-2379 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/high-throughput-chemical-biology">Mark Bradley</a></div></li><li  class="menu-3298 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/pericytes-hematopoietic-and-heart-development-and-injury">Mihaela Crisan</a></div></li><li  class="menu-2360 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/epithelial-stem-cells-tissue-renewal-and-cancer">Nick Barker</a></div></li><li  class="menu-2368 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/immune-regeneration-and-modulation">Paul Travers</a></div></li><li  class="menu-2365 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/molecular-membrane-biology">Rory Duncan</a></div></li><li  class="menu-2350 depth-3" title=""><div class="menu-item-wrapper"><a href="/research/group/stem-cells-and-regenerative-neurology" title="">Siddharthan Chandran</a></div></li><li  class="last menu-2362 depth-3"><div class="menu-item-wrapper"><a href="/research/associate/chromosomes-and-gene-expression">Wendy Bickmore</a></div></li></ul></div></li><li  class="last menu-2341 depth-2" title=""><div class="menu-item-wrapper"><a href="/research/publications" title="">CRM publications</a></div></li></ul></div></li><li  class="has-children menu-1938 depth-1" title=""><div 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building and other facilities including GMP cell therapy, FACS, flow cytometry, cell sorting, imaging, transgenics, tissue culture, histology, and research tools of the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">Facilities</a><ul><li  class="first menu-3137 depth-2"><div class="menu-item-wrapper"><a href="/facilities/imaging">Imaging</a></div></li><li  class="menu-3139 depth-2"><div class="menu-item-wrapper"><a href="/facilities/flow-cytometry">Flow cytometry</a></div></li><li  class="menu-3138 depth-2"><div class="menu-item-wrapper"><a href="/facilities/gmp-cell-therapy">GMP cell therapy</a></div></li><li  class="menu-3145 depth-2"><div class="menu-item-wrapper"><a href="/facilities/ccbn">CCBN</a></div></li><li  class="menu-3141 depth-2"><div class="menu-item-wrapper"><a href="/facilities/transgenics">Transgenics</a></div></li><li  class="menu-3142 depth-2"><div class="menu-item-wrapper"><a href="/facilities/tissue-culture">Tissue culture</a></div></li><li  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menu-2033 depth-2"><div class="menu-item-wrapper"><a href="/join-us/phd-training">PhD training</a><ul><li  class="first menu-2305 depth-3" title="Stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-structure" title="Stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD structure</a></div></li><li  class="menu-2307 depth-3" title="Videos and testimonials from PhD student at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/what-our-phd-students-say" title="Videos and testimonials from PhD student at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">What our PhD students say</a></div></li><li  class="menu-2308 depth-3" title="Available stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-opportunities" title="Available stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD opportunities</a></div></li><li  class="menu-2309 depth-3" title="Funding and finance opportunities for stem cell and regenerative medicine PhD studentships at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-funding-and-finance" title="Funding and finance opportunities for stem cell and regenerative medicine PhD studentships at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD funding and finance</a></div></li><li  class="menu-2037 depth-3" title="How to apply for stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/how-apply-phd" title="How to apply for stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">How to apply for a PhD</a></div></li><li  class="menu-2310 depth-3" title="Stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-web-resources" title="Stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD web resources</a></div></li><li  class="menu-2038 depth-3" title="Studying in the city of Edinburgh."><div class="menu-item-wrapper"><a 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													<h2>Diseases we study</h2>
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										Liver disease and cancer									</h1>
																							
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					<div class="field-item even"><p>The field of liver disease is wide and varied. It encompasses acute liver failure, fibrosis, cirrhosis and liver cancers such as cholangiocarcinoma (bile duct cancer).</p>
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<li><a href="/node/1018/#LiverIntro">Introduction</a></li>
<li><a href="/node/1018/#LiverWork">Work at CRM</a></li>
<li><a href="/node/1018/#LiverFAQ">Frequently Asked Questions - Prof Stuart Forbes</a></li>
<li><a href="/macrophage-cell-therapy-liver-cirrhosis">Macrophage Cell Therapy for Liver Cirrhosis</a></li>
</ul>
<h2><a id="LiverIntro"></a>Introduction</h2>
<p>Chronic liver disease is the 5th largest cause of death in the UK, and is common worldwide. Chronic damage leads to scarring and eventually cirrhosis which can lead to liver failure and ultimately liver cancer. Although liver transplantation is a cure for severe liver disease there are insufficient numbers of suitable organs. Furthermore liver transplantation results in the need for lifelong immunosuppression. Understanding and improving how the liver regenerates, and developing alternatives to liver transplantation is therefore a priority of our research at the MRC Centre for Regenerative Medicine.</p>
<p>The liver is a highly regenerative organ, which can regrow even after 70% of its volume has been removed. Damage to the liver occurs from many causes including genetic diseases, viral infections, immune mediated diseases, obesity, excessive alcohol intake and drug overdoses. If the damage is too severe then liver failure can occur.</p>
<p>Chronic damage also increases the chance of liver cancers developing. The bile ducts are a network of tubes that drain toxins from the liver. Bile duct cancer – known as cholangiocarcinoma – affects around a 1000 patients a year in the UK. It is often diagnosed at an advanced stage, which makes it very difficult to treat with surgery and cholangiocarcinoma typically does not respond to chemotherapy. Researchers are trying to understand what drives the growth of these cancers so we can develop new treatments.</p>
<h2><a id="LiverWork"></a>Work at CRM</h2>
<ul>
<li><a href="/research/group/liver-tissue-development-and-engineering">Dr David Hay</a> focuses on generating hepatocytes from embryonic and induced pluripotent stem cells. He has developed a technology to produce large quantities of hepatocytes in a dish, which can be used to develop novel models of drug-induced liver injury and Hepatitis C virus infection. In the long run, these cells might represent a source for supporting failing human liver function. Dr Hay also collaborates with <a href="/research/associate/high-throughput-chemical-biology">Prof Mark Bradley</a> at the University of Edinburgh’s School of Chemistry. Together they investigate chemical substances such as particular synthetic surfaces that can provide support for stem cells and help them turn into liver cells.</li>
<li><a href="/research/group/liver-stem-cells-and-regeneration">Prof Stuart Forbes</a> and his team work to understand the role of liver progenitor cells (HPCs) in the damaged liver. They aim to identify the signals that control the repair of damaged tissue, which will offer targets for drugs to stimulate healing of the liver. They also study the use of stem cells to repair the liver following transplantation by improving liver regeneration and removing scar tissue.</li>
</ul>
<h2><a id="LiverFAQ"></a>Frequently Asked Questions - Prof Stuart Forbes</h2>
<p>Prof Stuart Forbes introduces his research at the MRC Centre for Regenerative Medicine in the video below.</p>
<div class="media-youtube-video media-youtube-15 media-element file-500-px-wide" data-file_info="%7B%22fid%22:%22619%22,%22view_mode%22:%22500_px_wide%22,%22fields%22:%7B%22format%22:%22500_px_wide%22%7D,%22type%22:%22media%22%7D">
<iframe width="500" height="281" title="Prof Stuart Forbes - Liver Stem Cells &amp; Regeneration" class="media-youtube-player" src="//www.youtube.com/embed/5VDMYl0o0Uo?wmode=opaque" frameborder="0" allowfullscreen="">Video of Prof Stuart Forbes - Liver Stem Cells &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Regeneration</iframe></div>
<ol>
<li>
<h4>Are you involved in clinical trials?</h4>
<p>Yes. Together with <a href="https://www.birmingham.ac.uk/staff/profiles/iandi/newsome-philip.aspx">Prof Philip Newsome</a> (Birmingham University) the Forbes lab has developed and undertaken the so-called ‘REALISTIC’ study (REPEATED AUTOLOGOUS INFUSIONS OF STEM CELLS IN CIRRHOSIS): a multicentre, phase II, open label, randomised controlled trial of repeated infusions of autologous CD133+ bone marrow stem cells mobilized by G-CSF in patients with cirrhosis. This trial runs in Edinburgh, Birmingham and Nottingham and has finished recruiting 81 patients. The results of this trial are not known yet as monitoring patients as part of the follow-up phase is ongoing. More information about the trial can be found <a href="https://bmjopen.bmj.com/content/5/3/e007700.full">here</a>.  The trial was registered at <a href="http://www.isrctn.com">Current Controlled Trials</a> on 18 November 2009 (ISRCTN number 91288089, EuDRACT number 2009-010335-41).</p></li>
<li>
<h4>Are you currently recruiting for other clinical trials?</h4>
<p>The Forbes lab have a new Clinical Trial commencing in 2016. 68-77 patients for this single centre, safety, feasibility and efficacy phase I to phase II study will be recruited locally (Edinburgh area) through the UK's National Health Service (NHS). This study is called 'MATCH 0.1', (Macrophage Therapy for Liver Cirrhosis).</p></li>
<li>
<h4>Can I take part in a future clinical trial?</h4>
<p>Should the Forbes lab take part in future clinical trials, patients will be recruited locally through the UK’s National Health System (NHS).</p></li>
<li>
<h4>When will this stem cell based treatment become available?</h4>
<p>Unfortunately there are many research questions still unanswered. Also, the vigorous clinical trial process is strictly regulated to make sure treatments are effective and safe for patients. There are still a number of regulatory hurdles to pass before a treatment becomes available in the clinic. This is quite a long process unfortunately, it can easily take 10-15 years.</p></li>
<li>
<h4>Can you give me medical advice?</h4>
<p>Unfortunately Prof Stuart Forbes and his team cannot give medical advice or recommend on a specific stem cell therapy or trial. We do recommend you take advice of your local healthcare team.</p></li>
<li>
<h4>Where can I get more information?</h4>
<p>• Bile Duct Cancer: there is a very good charity called the <a href="https://ammf.org.uk/">AMMF Cholangiocarcinoma Charity</a>. They offer support, advice and are well placed to provide you with up-to-date information. <br />• Liver disease: the <a href="https://britishlivertrust.org.uk/">British Liver Trust</a> provides very accurate and balanced information. They also have support groups and can help you find a group near you. <br />• Stem cells and clinical trials: please see the <a href="/about-stem-cells/diseases-we-study/information-patients">Patients section</a> on our website and follow the links.</p></li>
<li>
<h4>If I can’t take part in a clinical trial, can I help in other ways?</h4>
<p>Yes. Philanthropy in research is increasingly important as funding streams change. It is thanks to people like you that we are able to attract the brightest minds and provide world-class research facilities. If you wish to support the Forbes lab and their research efforts to better understand liver disease and cancer and help develop treatments, you can <a href="/donate-introduction">donate to CRM</a> or to our dedicated ‘<a href="https://donate.ed.ac.uk/portal/public/donate/donate.aspx?destination=LiverBileDuctCancer">Liver and Bile Duct Cancer Fund</a>’. Your contribution and support is much appreciated.</p></li>
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