Abstract
Vascularized composite allotransplantation opens new possibilities in reconstructive transplantation such as hand or face transplants. Lifelong immunosuppression and its side-effects are the main drawbacks of this procedure. Mesenchymal stem cells (MSCs) have clinically useful immunomodulatory effects and may be able to reduce the burden of chronic immunosuppression. Herein, we assess and compare characteristics and immunomodulatory capacities of bone marrow- and adipose tissue-derived MSCs isolated from the same human individual across defined human leukocyte antigen (HLA) barriers. Samples of omental (o.) adipose tissue, subcutaneous (s.c.) adipose tissue, and bone marrow aspirate from 10 human organ donors were retrieved and MSCs isolated. Cells were characterized by flow cytometry and differentiated in three lineages: adipogenic, osteogenic, and chondrogenic. In mixed lymphocyte reactions, the ability of adipose-derived mesenchymal stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) to suppress the immune response was assessed and compared within individual donors. HLA mismatched or mitogen stimulations were analyzed in co-culture with different MSC concentrations. Supernatants were analyzed for cytokine contents. All cell types, s.c.ASC, o.ASC, and BMSC demonstrated individual differentiation potential and cell surface markers. Immunomodulating effects were dependent on dose and cell passage. Proliferation of responder cells was most effectively suppressed by s.c.ASCs and combination with BMSC resulted in highly efficient immunomodulation. Immunomodulation was not cell contact-dependent and cells demonstrated a specific cytokine secretion. When human ASCs and BMSCs are isolated from the same individual, both show effective immunomodulation across defined HLA barriers in vitro. We demonstrate a synergistic effect when cells from the same biologic system were combined. This cell contact-independent function underlines the potential of clinical systemic application of MSCs.
Highlights
Vascularized composite allotransplantation (VCA) is an emerging field, expanding the armamentarium for reconstructive surgery after severe trauma, illness, or other causes of extended tissue loss
The overall goal of this study was to analyze and character ize Mesenchymal stem cells (MSCs) isolated from s.c.ASCs, o.ASCs, and bone marrow aspirate retrieved form the same biological system and com pare between 10 human tissue donors
Slight differences were identified in the hematopoietic marker CD34 which did not reach statistical significance (s.c.ASC vs. BMSC p = 0.31; s.c.ASC vs. o.ASC p = 0.15)
Summary
Vascularized composite allotransplantation (VCA) is an emerging field, expanding the armamentarium for reconstructive surgery after severe trauma, illness, or other causes of extended tissue loss. Sex, and skin color [3], general solid organ matching criteria such as cytomegalovirus status, patient sensitization [4], and human leukocyte antigen (HLA) typing play an important role in graft allocation and patient selection. The grade of HLA mismatch has been shown to increase the risk of acute rejection [5] in hand transplant patients and represents one of the biggest hurdles in VCA due to the shortage of donors. Acute rejection in VCA is unique in its char acteristics [6] and occurs in a much higher frequency compared with solid organ transplantation [7]. We assess and compare characteristics and immunomodulatory capacities of bone marrow- and adipose tissue-derived MSCs isolated from the same human individual across defined human leukocyte antigen (HLA) barriers
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