Clinical Implication of Allogenic Implantation of Adipogenic Differentiated Adipose‐Derived Stem Cells

• Published in: Stem cells translational medicine Vol. 3; no. 11; pp. 1312 - 1321
• Main Authors: Kim, Inok, Bang, Sa Ik, Lee, Sung Koo, Park, Soo Young, Kim, Mihyung, Ha, Hunjoo
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01.11.2014; Oxford University Press
• Subjects: Adipocytes; Adipogenesis; Adipogenic differentiated ASCs; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adipose-derived stem cells; Allogenic transplantation; Allografts; Animals; Autologous transplantation; Cell culture; Cell Differentiation; Clinical trials; Defects; Flow cytometry; Growth factors; Heterografts; Humans; Immune response; Immunogenicity; Major histocompatibility complex; Male; Mice; Mice, Inbred BALB C; Stem Cell Transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Studies; Therapeutic applications; Tissue engineering; Tissue-Specific Progenitor and Stem Cells; Transplants & implants; Allogenic transplantation; Adipose-derived stem cells; Adipogenic differentiated ASCs; Immunogenicity; Autologous transplantation
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2014-0109

The goal of this study was to investigate the immunological properties of adipogenic differentiated adipose‐derived stem cells (ASCs) to evaluate their suitability for allogenic applications, including in vitro, in vivo, and clinical applications, through comprehensive studies. The allogenic immune response of adipogenic differentiated ASCs was investigated by flow cytometry, mixed lymphocyte culture, and allogenic implantation. The results suggest that adipogenic differentiated ASCs can be used as a universal donor for soft‐tissue engineering in major histocompatibility complex‐mismatched recipients. We recently reported that autologous adipogenic differentiated adipose‐derived stem cells (ASCs) can potentially be used as an effective and safe therapy for soft‐tissue regeneration. In the present study, we investigated whether adipogenic differentiated ASCs can be used for allogenic applications to enlarge their therapeutic use. The allogenic immune response of adipogenic differentiated ASCs was investigated by flow cytometry and mixed lymphocyte culture. To determine whether adipogenic differentiated ASCs can form new adipose tissue without immune rejection, these cells were implanted subcutaneously into allo‐ or xenogenic recipient mice. In addition, the safety of the allogenic implantation of adipogenic differentiated ASCs was explored in a phase I clinical study. Adipogenic differentiated ASCs do not express major histocompatibility complex (MHC) class II molecules and costimulatory molecules, and the expression levels of MHC class I decreased after differentiation. In addition, these cells do not elicit an immune response against MHC‐mismatched allogenic lymphocytes and formed new adipose tissue without immune rejection in the subcutaneous region of MHC‐mismatched mice. Moreover, these cells did not induce clinically significant local and systemic immune responses or adverse events in the subcutaneous region of donor‐independent healthy subjects. These results suggest that adipogenic differentiated ASCs can be used as a “universal donor” for soft‐tissue engineering in MHC‐mismatched recipients.