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

Abstract

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.

The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy

“…Increasingly, however, in vivo studies report that allo-MSCs are not fully immune privileged and probably cause an immune response despite the immunosuppressive properties and low immunogenicity of MSCs being documented both in vivo and in vitro. Currently, different research groups have obtained inconsistent or even contradictory results on the therapeutic effects of allo-MSCs in various studies [ 18 – 21 ]. Therefore, the in vivo immunogenicity of allo-MSCs and the relationship between immunogenicity and their protective effects remains to be determined.…”

“…There are two types of topical administration: intralesional injection (e.g., intracranial, intracerebral, subcutaneous) and local vascular injection (e.g., superior vena cava, mesenteric blood vessels, coronary artery). Compared with systemic administration, topical administration routes may have a common advantage in that MSCs arrive directly at the target tissue with little loss during migration [ 18 , 22 ]. It was demonstrated that allo-MSCs loaded onto cancellous bone granules have a similar efficacy to auto-MSCs for bone regeneration in bone defect models [ 23 ].…”

Notch Signaling Pathway Regulates Angiogenesis via Endothelial Cell in 3D Co‐Culture Model

“…Adipose‐derived stromal cells (ASCs) isolated from adipose tissues in vitro have adipogenic (Kim, ), osteogenic (Gong, ), chondrogenic (Mellor, ), myogenic (Lee and Kemp, ), cardiomyogenic (Gwak, ), angiogenic (Mehrabani, ), epithelial (Nieto Miguel, ), and neurogenic (Safford, ) properties and remain these properties after serial passages (Zhu, ). And human adipose tissues are ubiquitous, abundance, rich in ASCs, and easy to obtain with little operative site morbidity and patient discomfort.…”

The Role of Adipose-Derived Stem Cells, Dermal Regenerative Templates, and Platelet-Rich Plasma in Tissue Engineering-Based Treatments of Chronic Skin Wounds

“…In particular, ASCs express a low level of major histocompatibility complex (MHC) class I molecules and do not express MHC class II and costimulatory molecules, such as CD40, CD80 (B7-1), and CD86 (B7-2) [19][20][21]. Interestingly, also adipogenic-differentiated ASCs have no immunogenicity and are clinically safe [22]. Based on these properties, ASCs have generated great interest and are perceived as the most preferred cell type for tissue engineering and regenerative medicine [23].…”