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.

Public Health Relevance

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

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource Grants (P40)
Project #
5P40OD011050-12
Application #
8677989
Study Section
Special Emphasis Panel (ZTR1-CM-6 (01))
Program Officer
Mirochnitchenko, Oleg
Project Start
2013-06-15
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
12
Fiscal Year
2014
Total Cost
$973,959
Indirect Cost
$306,864
Name
Texas A&M University
Department
None
Type
Schools of Medicine
DUNS #
835607441
City
College Station
State
TX
Country
United States
Zip Code
77845
Hoffman, Michael D; Van Hove, Amy H; Benoit, Danielle S W (2014) Degradable hydrogels for spatiotemporal control of mesenchymal stem cells localized at decellularized bone allografts. Acta Biomater 10:3431-41
Prockop, Darwin J; Prockop, Susan E; Bertoncello, Ivan (2014) Are clinical trials with mesenchymal stem/progenitor cells too far ahead of the science? Lessons from experimental hematology. Stem Cells 32:3055-61
Bartosh, Thomas J; Ylostalo, Joni H (2014) Preparation of anti-inflammatory mesenchymal stem/precursor cells (MSCs) through sphere formation using hanging-drop culture technique. Curr Protoc Stem Cell Biol 28:Unit 2B.6.
Watanabe, Jun; Shetty, Ashok K; Hattiangady, Bharathi et al. (2013) Administration of TSG-6 improves memory after traumatic brain injury in mice. Neurobiol Dis 59:86-99