Donor age negatively affects the immunoregulatory properties of both adipose and bone marrow derived mesenchymal stem cells

Lehao W Wu, Yen-Ling Wang, Joani M Christensen, Saami Khalifian, Stefan Schneeberger, Giorgio Raimondi, Damon S Cooney, W P Andrew Lee, Gerald Brandacher
Transplant Immunology 2014, 30 (4): 122-7

PURPOSE: Age negatively impacts the biologic features of mesenchymal stem cells (MSCs), including decreased expansion kinetics and differentiation potential. Clinically, donor-age may be within a wide spectrum; therefore, investigation of the role of donor's age on immunoregulatory potential is of critical importance to translate stem cell therapies from bench to bedside.

METHODS: Adipose and bone marrow derived MSCs (ASCs and BMSCs) were isolated in parallel from Lewis and Brown Norway rats of young (less than 4-week old) and senior groups (older than 15-month). The presentation of cells and time required for growth to 90% confluence was recorded. FACS sorting based on the expression of CD90 and CD29 double positive and CD45 CD11 double negative quantified the proportions of MSCs. After expansion, ASCs and BMSCs from different age groups were co-cultured in mixed lymphocyte reaction (MLR; Lewis vs. Brown Norway) assays. The suppression of CD3(+)CD4(+) and CD3(+)CD8(+) T cell populations by different sources of MSCs were compared.

RESULTS: The kinetics of cell growth was slower in old animals (17.3±2days) compared with young animals (8.8±3days), and cell morphology was irregular and enlarged in the senior groups. The yield of MSCs by FACS sorting was significantly higher in young groups compared to senior groups (p<0.02). With regard to immunoregulatory potential, senior ASCs failed to induce any CD3(+)CD4(+) T cell suppression (p>0.05). In addition, young BMSCs-induced suppression was more prominent than seniors (p<0.05).

CONCLUSIONS: Donor age should be taken into consideration when using recipient MSC of either bone marrow or adipose origin in clinical applications.

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