This a competing renewal application (Type 2) for a Center to prepare adult stem/progenitor cells from the bone marrow of human volunteers and rodents, define the quality of the cells, and then distribute them to multiple investigators. The adult stem/progenitor cells we prepare were originally referred to as fibroblastic colony-forming-units, then as marrow stromal cells in the hematological literature, subsequently as mesenchymal stem cells, and most recently as multipotent mesenchymal stromal cells or MSCs. Since the last competitive renewal, we made 627 shipments of 1,075 vials of frozen MSCs to over 280 scientists of whom 157 are funded by 18 NIH Institutes. We have received over 140 Letters of Support.
The Aims are: (1) To continue to produce standardized preparations of human MSCs (hMSCs) for distribution to other investigators. We will transduce some of the hMSCs with lentiviruses to express genes useful in tracking the cells both in culture and in vivo: with cytoplasmic green fluorescent protein (GFP), mitochondrial red fluorescent protein (MitoRed) and luciferase. (2) To continue to provide similar preparations of mouse MSCs (mMSCs) for distribution to other investigators. (3) To continue to provide similarly characterized preparations of rat MSCs (rMSCs) for distribution to other investigators. We will continue to prepare rMSCs from other rat strains and from transgenic rats ubiquitously expressing GFP as a marker for experiments in culture and in vivo. (4) In exploratory research (up to 10% of allocated funds), we will compare the genes expressed by different standard preparations of hMSCs and hMSCs pre-activated in culture by cytokines using microarrays, qRT-PCR and ELISAa for secreted factors. The data will be analyzed to identify the preparations with the highest levels of expression of anti-inflammatory and immune regulatory genes. The results will be provided to recipients of the hMSCs and scientists will be encouraged to compare preparations that the data suggest may vary in efficacy in the systems they are testing. We will provide assistance from a collaborating expert in bioinformatics in evaluating the data.
There is now great interest in mesenchymal stem/progenitor cells (MSCs) with over 17,000 citations in the common search engine (PubMed) and over 150 registered clinical trials (www.clinicaltrials.gov). However, there are differences in the protocols to prepare the cells and the final quality of the cells. This Centr provides investigators with thoroughly characterized MSCs that they can use as a reference standard for their experiments
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|Prockop, Darwin J; Oh, Joo Youn; Lee, Ryang Hwa (2017) Data against a Common Assumption: Xenogeneic Mouse Models Can Be Used to Assay Suppression of Immunity by Human MSCs. Mol Ther 25:1748-1756|
|Mittal, Manish; Tiruppathi, Chinnaswamy; Nepal, Saroj et al. (2016) TNF?-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung injury. Proc Natl Acad Sci U S A 113:E8151-E8158|
|Prockop, Darwin J (2016) Inflammation, fibrosis, and modulation of the process by mesenchymal stem/stromal cells. Matrix Biol 51:7-13|
|Bazhanov, Nikolay; Ylostalo, Joni H; Bartosh, Thomas J et al. (2016) Intraperitoneally infused human mesenchymal stem cells form aggregates with mouse immune cells and attach to peritoneal organs. Stem Cell Res Ther 7:27|
|Xie, Jie; Broxmeyer, Hal E; Feng, Dongni et al. (2015) Human adipose-derived stem cells ameliorate cigarette smoke-induced murine myelosuppression via secretion of TSG-6. Stem Cells 33:468-78|
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