The cells have been variously referred to as colony-forming fibroblasts, mesenchymal stem cells, or marrow stromal cells (MSCs), have attracted increasing interest both for their biological properties as multi-potential stem-like cells and their potential use for cell and gene therapy. And their potential use for cell and gene therapy. However, a major problem in the field has been that reproducible conditions for isolation and expansion of the cells in culture have not been defined. The overall aim of the present proposal is to develop effective conditions for the isolation and expansion of human hMSCs (hMSCs) in cultured based on three recent observations made in our laboratory: (a) We have developed culture conditions whereby hMSCs can be expanded over 10/8-fold without significant loss in replicative capacity. (b) We have found that replication of hMSCs in culture is regulated autocrine/paracrine factors that can be recovered from the culture medium. (c) We have identified a sub-population of small granular cells in cultures of hMSCs that are highly replicative and appear to be the earliest progenitors in the cultures.
The Specific Aims of this proposal are: (1) Determine whether the highly replicative cells we have obtained after 10/8-fold expansion of hMSCs retain their multi- potentiality to differentiate into osteoblasts, chrondrocytes and adipocytes. (2) Isolate and characterize the secreted factors that regulate replication of hMSCs in culture. (3) Isolate the small, granular, and highly replicative cells we have identified in cultures of hMSCs and define their surface epitopes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR047796-02
Application #
6375382
Study Section
Special Emphasis Panel (ZAR1-AAA-A (M1))
Program Officer
Sharrock, William J
Project Start
2000-09-30
Project End
2002-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$74,250
Indirect Cost
Name
Tulane University
Department
Genetics
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Oskowitz, Adam Z; Penfornis, Patrice; Tucker, Alan et al. (2011) Drosha regulates hMSCs cell cycle progression through a miRNA independent mechanism. Int J Biochem Cell Biol 43:1563-72
Oskowitz, Adam; McFerrin, Harris; Gutschow, Miriam et al. (2011) Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic. Stem Cell Res 6:215-25
Sanchez, Cecilia G; Penfornis, Patrice; Oskowitz, Adam Z et al. (2011) Activation of autophagy in mesenchymal stem cells provides tumor stromal support. Carcinogenesis 32:964-72
Sanchez, Cecilia; Oskowitz, Adam; Pochampally, Radhika R (2009) Epigenetic reprogramming of IGF1 and leptin genes by serum deprivation in multipotential mesenchymal stromal cells. Stem Cells 27:375-82
Spees, Jeffrey L; Whitney, Mandolin J; Sullivan, Deborah E et al. (2008) Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension. FASEB J 22:1226-36
Oskowitz, Adam Z; Lu, Jun; Penfornis, Patrice et al. (2008) Human multipotent stromal cells from bone marrow and microRNA: regulation of differentiation and leukemia inhibitory factor expression. Proc Natl Acad Sci U S A 105:18372-7
Pochampally, Radhika R; Ylostalo, Joni; Penfornis, Patrice et al. (2007) Histamine receptor H1 and dermatopontin: new downstream targets of the vitamin D receptor. J Bone Miner Res 22:1338-49
Ylostalo, Joni; Smith, Jason R; Pochampally, Radhika R et al. (2006) Use of differentiating adult stem cells (marrow stromal cells) to identify new downstream target genes for transcription factors. Stem Cells 24:642-52
Gregory, Carl A; Perry, Anthony S; Reyes, Emigdio et al. (2005) Dkk-1-derived synthetic peptides and lithium chloride for the control and recovery of adult stem cells from bone marrow. J Biol Chem 280:2309-23
Spees, Jeffrey L; Gregory, Carl A; Singh, Harpreet et al. (2004) Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol Ther 9:747-56

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