Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells
Stem Cell Research and Therapy
Gimble et al. Stem Cell Research & Therapy 2010, 1:19 http://stemcellres.com/content/1/2/19
Jeffrey M Gimble1,2*, Farshid Guilak3 and Bruce A Bunnell4,5
Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of
adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture- expanded, adipose-derived stromal/stem cells in vitroand in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I–III clinical evidence using autologous adipose- derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated.
The application of ASCs and SVF cells is still in its infancy and the field has made progressive advances towards clinical applications. In general, the clinical investigators who have published their findings have taken pains to address the important regulatory questions before advancing from animal models to patients. These researchers are to be applauded for treating the regulatory guidelines not as roadblocks but as opportunities for documenting the safety of their cell-based products. Still, there have not been many published safety studies addressing the legitimate concerns of regulatory authorities that include the following questions.
Can human ASCs and SVF cell implants cause tumors either directly through transformation or indirectly by promoting the growth of endogenous tumor cells? At least one manuscript has reported that human ASCs expanded long term in vitro will cause sarcomas when implanted in vivo in an immunodeficient mouse .
Has a current good manufacturing practice scheme of manufacture been developed for the cell products? While this information must be available to support existing clinical trials, details of standard operating protocols have not been made public. International standardization of ASCs and SVF cells would significantly advance clinical translation. Published definition of the cell identity with a panel of surface antigens and establishment of universally applied quality assurance/ quality control testing criteria would benefit the fledgling adipose stem cell community.
As discussed above, there is no shortage of diseases – both acute and chronic – where adipose-derived cell therapies could have a potential clinical impact. The next steps will include documenting the reproducibility of the current preclinical and clinical findings, and controlled testing of the safety and efficacy of ASCs and SVF cells in a range of human conditions. In another decade, we postulate that the cells will prove beneficial to some, but not all, of the disease models tested. We expect initial successes to come in applications relating to acute disorders; however, we are hopeful that chronic diseases amenable to SVF cell therapy or ASC therapy will also be identified.