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With the current pace of progress, in a few years' time, the field of stem cell\u2010based therapy should be able to respond to the market demand for safe, robust and clinically efficient stem cell\u2010based therapeutics. Due to the limited number of stem cells that can be obtained from a single donor, one of the major challenges on the roadmap for regulatory approval of such medicinal products is the expansion of stem cells using Good Manufacturing Practices (GMP)\u2010compliant culture systems. In fact, manufacturing costs, which include production and quality control procedures, may be the main hurdle for developing cost\u2010effective stem cell therapies. Bioreactors provide a viable alternative to the traditional static culture systems in that bioreactors provide the required scalability, incorporate monitoring and control tools, and possess the operational flexibility to be adapted to the differing requirements imposed by various clinical applications. Bioreactor systems face a number of issues when incorporated into stem cell expansion protocols, both during development at the research level and when bioreactors are used in on\u2010going clinical trials. This review provides an overview of the issues that must be confronted during the development of GMP\u2010compliant bioreactors systems used to support the various clinical applications employing stem cells.<\/jats:p>","DOI":"10.1002\/biot.201200373","type":"journal-article","created":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T08:29:19Z","timestamp":1366964959000},"page":"644-654","source":"Crossref","is-referenced-by-count":100,"title":["Bioreactor design for clinical\u2010grade expansion of stem cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Francisco F.","family":"dos Santos","sequence":"first","affiliation":[]},{"given":"Pedro Z.","family":"Andrade","sequence":"additional","affiliation":[]},{"given":"Cl\u00e1udia Lobato","family":"da Silva","sequence":"additional","affiliation":[]},{"given":"Joaquim M.S.","family":"Cabral","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2013,4,26]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.04.018"},{"key":"e_1_2_9_3_2","first-page":"24","article-title":"Streamlining cell therapy manufacture \u2013 from clinical to commercial scale.","volume":"10","author":"Davie N. 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