In Vivo Distribution of Human Adipose-Derived Mesenchymal Stem Cells in Novel Xenotransplantation Models

Abstract

The potential for human adipose-derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: nonobese diabetic/severe combined immunodeficient (NOD/SCID), nude/NOD/SCID, and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein was introduced into purified AMSC via retroviral vectors to assist in identification of cells after transplantation. Transduced cells were administered to sublethally irradiated immune-deficient mice through i.v., intraperitoneal, or subcutaneous injection. Up to 75 days after transplantation, tissues were harvested and DNA polymerase chain reaction (PCR) was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human ␤-globin and murine rapsyn primers assessed the contribution of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a recipient allowed rapid identification of human cells in the murine tissues, using an enzyme reaction that was independent of surface protein expression or transduction with an exogenous transgene. For up to 75 days after transplantation, donor-derived cells were observed in multiple tissues, consistently across the various administration routes and independent of transduction parameters. Tissue localization studies showed that the primary MSC did not proliferate extensively at the sites of lodgement. We conclude that human AMSC represent a population of stem cells with a ubiquitous pattern of tissue distribution after administration. AMSC are easily obtained and highly amenable to current transduction protocols for retroviral transduction, making them an excellent avenue for cell-based therapies that involve a wide range of end tissue targets. STEM CELLS 2007;25:220 -227

Stromal Cells Protect against Acute Tubular Injury via an Endocrine Effect

“…At the end of the second passage or at 5 to 8 wk of expansion, BMSC were used for transplantation or generation of conditioned medium (Supplementary Figure 1). AdSC were purified from abdominal adipose samples by the method of Meyerrose et al 34 Briefly, abdominal adipose tissue was harvested at the same time as the bone marrow, and samples were washed thoroughly with PBS followed by digestion in 0.075% collagenase (Sigma) for 30 min at 37°C. Digestion was stopped with IMDM media (Invitrogen) containing 10% fetal bovine serum (FBS).…”

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

“…Thus, MSCs are thought to be the key in maintaining the bone marrow microenvironment. Various mesenchymal tissues such as s.c. fat also contain MSCs (5).…”

Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis

“…[37][38][39][40] It is a matter of debate, whether MSCs may differentiate into the tissues of interest, although this has been shown in various animal models. 23,41,42 In some studies, the beneficial effect of MSCs rather was attributed to the secretion of cytokines and growth factors at the site of injury. 43,44 Obviously, for the use of MSCs in regenerative medicine, a sustained engraftment is Figure 4 Mesenchymal stromal cells (MSCs) can be expanded from individuals with osteonecrosis from a bone marrow biopsy at a distant site in platelet lysate-supplemented culture media.…”