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Updated: Apr 20, 2026
Repair of a Critical-sized Calvarial Defect Model Using Adipose-derived Stromal Cells Harvested from Lipoaspirate
Published on: October 31, 2012
Adipose-derived stromal cells promote allograft tolerance induction
Thomas A Davis1, Khairul Anam2, Yelena Lazdun2
1Regenerative Medicine Department, Operational and Undersea Medicine Directorate, Naval Medical Research Center, Silver Spring, Maryland, USA; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Department of Medicine and Surgery Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA; LaCell, LLC, New Orleans, Louisiana, USA thomas.davis1@med.navy.mil.
Adipose-derived stromal/stem cells (ASCs) combined with donor bone marrow cells (BMCs) promote long-term skin allograft survival by inducing immune tolerance. This approach may reduce reliance on immunosuppression for vascular composite allotransplants (VCAs).
Area of Science:
- Immunology
- Regenerative Medicine
- Transplantation Science
Background:
- Vascular composite allotransplants (VCAs) offer reconstructive solutions for combat-wounded individuals but face challenges with skin graft rejection.
- Long-term immunosuppression for VCAs carries significant risks and complications.
- Adipose-derived stromal/stem cells (ASCs) possess immunomodulatory properties and are readily available.
Purpose of the Study:
- To investigate the efficacy of ASCs in facilitating long-term skin allograft survival.
- To determine if ASCs, alone or with donor bone marrow cells (BMCs), can induce immune tolerance for allografts.
- To explore a potential alternative to prolonged immunosuppression in VCA protocols.
Main Methods:
- Human ASCs were isolated from adipose lipoaspirate.
- Full-thickness skin grafts were transplanted from BALB/c to C57BL/6 mice under a minimal conditioning regimen (anti-CD4/CD8 antibodies and low-dose busulfan).
- ASCs were infused intravenously with or without donor BMCs post-transplantation.
Main Results:
- ASC and BMC coinfusion resulted in stable lymphoid and myeloid macrochimerism.
- This coinfusion led to the deletion of alloreactive T cells and expansion of regulatory T cells.
- Long-term allograft survival (>200 days) was achieved, with ASCs producing key immunoregulatory factors.
Conclusions:
- ASC and low-dose BMC coinfusion with minimal conditioning can induce long-term skin allograft acceptance.
- This strategy shows promise for developing advanced VCA protocols with reduced immunosuppression.
- Further studies in nonhuman primates are warranted to translate these findings for clinical application.
