Open AccessClinical‐Scale Expansion of a Mixed Population of Bone Marrow‐Derived Stem and Progenitor Cells for Potential Use in Bone Tissue Regeneration
Author(s) -
Dennis James E.,
Esterly Kelly,
Awadallah Amad,
Parrish Christopher R.,
Poynter Gregory M.,
Goltry Kristin L.
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0204
Subject(s) - progenitor cell , bone marrow , biology , stem cell , mesenchymal stem cell , cd90 , population , haematopoiesis , immunology , microbiology and biotechnology , ex vivo , in vivo , cd34 , medicine , environmental health
Preclinical and clinical studies have demonstrated the ability of bone marrow derived stem and progenitor cells to regenerate many tissues, including bone. Methods to expand or enrich progenitors from bone marrow are common; however, these methods include many steps not amenable to clinical use. A closed automated cell production culture system was developed for clinical‐scale ex vivo production of bone marrow‐derived stem and progenitor cells for hematopoietic reconstitution. The current study tested the ability of this bioreactor system to produce progenitor cells, termed tissue repair cells (TRC), possessing osteogenic potential. Three TRC formulations were evaluated: (a) cells cultured without exogenous cytokines (TRC); (b) cells cultured with exogenous cytokines (TRC‐C); and (c) an adherent subset of TRC‐C (TRC‐C Ad ). Starting human bone marrow mononuclear cells (BM MNC) and TRC products were characterized for the expression of cell surface markers, in vitro colony forming ability, and in vivo osteogenic potential. Results showed significant expansion of mesenchymal progenitors (CD90+, CD105+, and CD166+) in each TRC formulation. In vivo bone formation, measured by histology, was highest in the TRC group, followed by TRC‐C Ad and TRC‐C. The TRC product outperformed starting BM MNC and had equivalent bone forming potential to purified MSCs at the same cell dose. Post hoc analysis revealed that the presence of CD90+, CD105+, and CD166+ correlated strongly with in vivo bone formation scores ( r 2 > .95). These results demonstrate that this bioreactor system can be used to generate, in a single step, a population of progenitor cells with potent osteogenic potential. Disclosure of potential conflicts of interest is found at the end of this article.