Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies

Abstract

Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

“…Part of the beneficial effect of human AD-MSCs on CIA could lie in their potential capacity to repair the damaged joint tissue via differentiation (7,8). Efficient engraftment is a prerequisite for this stromal cell-based therapy.…”

“…Human and murine AD-MSCs were obtained essentially as described previously (8,18). Animal experimental protocols were approved by the Ethics Committee of the Spanish Council of Scientific Research.…”

“…Besides their capacity to differentiate into mesenchymal and nonmesenchymal cell lineages (7,8) and their potential clinical application for the repair of damaged tissues, several recent studies have shown that bone marrow-derived MSCs (BM-MSCs) regulate the immune response, including in vitro inhibition of T cell proliferation, B cell function, and dendritic cell maturation (9)(10)(11)(12)(13). Some researchers have reported the use of BM-MSCs to treat allograft rejection and acute graftversus-host disease as well as to alleviate experimental autoimmune encephalomyelitis, collagen-induced arthritis (CIA), and autoimmune myocarditis (11,(14)(15)(16)(17)(18)(19)(20).…”

“…Human MSCs obtained from subcutaneous adipose tissue (AD-MSCs) have recently emerged as an attractive alternative source of MSCs for cell therapy (7,8,10,21). Large amounts of human AD-MSCs can be easily obtained from lipoaspirates from healthy donors and rapidly expanded in vitro to generate a clinically effective dosage, and recent studies have reported that human AD-MSCs share some of the immunomodulatory properties that characterize the BM-MSCs (18,22,23).…”

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

“…The ASCs have shown to differentiate into muscle cells 22, 23. Human ASCs have also demonstrated paracrine function—immunomodulation, cytokine secretion, cytoprotection, and neovascularization 21, 24, 25.…”