Investigating treatments for adipose stem cells to maximize trophic factor production for cartilage regeneration

Abstract

Osteoarthritis is a leading cause of disability in the United States. Current methods of treatment aim to replace cartilage as opposed to regenerating tissue. There is interest in using stem cells as a source of growth factors to stimulate cartilage cells to produce extracellular matrix and an environment conducive to cartilage regeneration. The purpose of this study is to assess the effect of chemical and biological stimulation and a 3 dimensional structural environment on mRNA levels of adipose-derived stem cells in vitro and on cartilage regeneration in vivo. Adispose-derived stem cells (ASCs) were isolated from rats, microencapsulated, and treated with chondrogenic media. Chondrogenic media (CM) increased mRNA levels of many genes involved in chondrogenesis, including comp, acan, colX, and tgfb3, and decreased levels of the angiogenic factors fgf2 and vegfa. Microencapsulation increased mRNA levels of pthlh and tgfb3, and there was little difference on mRNA levels between calcium and barium crosslinks. The chemical components, ascorbic acid 2-phosphate (AA2P) and dexamethasone (Dex), and biological components, growth factors TGF-B1 and BMP-6, or chondrogenic media were assessed for their effect on ASC gene profile. Removing growth factors reduced mRNA levels of all genes assessed, whereas removing Dex and AA2P had variable effects on mRNA levels. ASCs were microencapsulated and preconditioned with CM prior to transplantation in a 2 mm cartilage defect in rats. The in vivo results displayed moderate cartilage infiltration into the defect. These data suggest that microencapsulation and treatment with CM can alter the gene profile to be conducive to cartilage regeneration and may regenerate cartilage in vivo.