Evolution and future prospects of adipose-derived immunomodulatory cell therapeutics.

Over the past two decades, tissue engineering and regenerative medicine have evolved from what many considered a theoretical science to what is now a clinical reality. Tissue engineering combines biomaterial scaffolds, growth factors and stem or progenitor cells to repair damaged tissues. Adipose tissue, an abundant and easily accessed tissue, is a potential source of stromal/stem cells for regenerative therapeutic applications.

Evaluation of cellular and humoral immune responses to allogeneic adipose-derived stem/stromal cells.

Adipose-derived mesenchymal stem or stromal cells (ASCs) are poised for clinical use in an allogeneic setting. Although ASCs have been shown to be nonimmunogenic by several laboratories, it is advisable for the investigator to confirm this for ASCs used in their studies due to variations in ASC production and the animal models in which they are used. We describe here the use of the mixed lymphocyte reaction (MLR) assay to determine immunogenicity and suppression by ASCs in vitro as well as assessing T cell responses to allogeneic ASC transplantation in vivo.

Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model.

Adipose-derived stem cells (ASCs) express a nonimmunogenic profile as shown by in vitro studies that demonstrate a lack of T cell proliferation to allogeneic ASCs as well as ASC-mediated suppression of mixed lymphocyte reactions. To determine whether these observations would translate in vivo, immune monitoring studies were carried out in conjunction with a rat spinal fusion study. ASCs derived from Fischer or ACI strain rats were loaded onto scaffolds and implanted in Fischer recipients that had undergone the following treatments: (1) No treatment; (2) Scaffold only; (3) Syngeneic ASCs+Scaffold; or (4) Allogeneic ASCs+Scaffold.

Acceleration of spinal fusion using syngeneic and allogeneic adult adipose derived stem cells in a rat model.

Posterolateral spinal fusion is the standard treatment for lumbar compression fractures. Adult adipose tissue-derived stem cells (ASCs) promote osteogenesis in vivo and in vitro. The hypothesis tested in this study was that syngeneic and allogeneic ASCs on a biomaterial scaffold composed of tricalcium phosphate and collagen I will accelerate spinal fusion in a rat model.

Immune properties of human umbilical cord Wharton's jelly-derived cells.

Cells isolated from Wharton's jelly, referred to as umbilical cord matrix stromal (UCMS) cells, adhere to a tissue-culture plastic substrate, express mesenchymal stromal cell (MSC) surface markers, self-renew, and are multipotent (differentiate into bone, fat, cartilage, etc.) in vitro. These properties support the notion that UCMS cells are a member of the MSC family.

T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression.

Human mesenchymal stem cells (MSCs) were evaluated for their ability to activate allogeneic T cells in cell mixing experiments. Phenotypic characterization of MSCs by flow cytometry showed expression of MHC Class I alloantigens, but minimal expression of Class II alloantigens and costimulatory molecules, including CD80 (B7-1), CD86 (B7-2), and CD40. T cells purified from peripheral blood mononuclear cells (PBMCs) did not proliferate to allogeneic MSCs.

Characterization and functionality of cell surface molecules on human mesenchymal stem cells.

We have characterized adhesion molecules on the surface of multipotential human mesenchymal stem cells (hMSCs) and identified molecules whose ligands are present on mature hematopoietic cells. Flow cytometric analysis of hMSCs identified the expression of integrins: alpha1, alpha2, alpha3, alpha5, alpha6, alphav, beta1, beta3, and beta4, in addition to ICAM-1, ICAM-2, VCAM-1, CD72, and LFA-3. Exposure of hMSCs to IL-1alpha, TNFalpha or IFNgamma up-modulated ICAM-1 surface expression, whereas only IFNgamma increased both HLA-class I and -class II molecules on the cell surface.