Abstract
Microencapsulating stem cells in injectable microbeads can enhance delivery and localization, but their ability to act as growth factor production sources is still unknown. To address this concern, growth factor mRNA levels and production from alginate microbeads with encapsulated human adipose stem cells (ASC microbeads) cultured in both growth and chondrogenic media (GM and CM) were measured over a two week period. Human ASCs in microbeads were either commercially purchased (Lonza) or isolated from six human donors and compared to human ASCs on tissue culture polystyrene (TCPS). The effects of crosslinking and alginate compositions on growth factor mRNA levels and production were also determined. Secretion profiles of IGF-I, TGF-β3 and VEGF-A from commercial human ASC microbeads were linear and at a significantly higher rate than TCPS cultures over two weeks. For human ASCs derived from different donors, microencapsulation increased pthlh and both IGF-I and TGF-β3 secretion. CM decreased fgf2 and VEGF-A secretion from ASC microbeads derived from the same donor population. Crosslinking microbeads in BaCl2 instead of CaCl2 did not eliminate microencapsulation's beneficial effects, but did decrease IGF-I production. Increasing the guluronate content of the alginate microbead increased IGF-I retention. Decreasing alginate molecular weight eliminated the effects microencapsulation had on increasing IGF-I secretion. This study demonstrated that microencapsulation can enhance chondrogenic growth factor production and that chondrogenic medium treatment can decrease angiogenic growth factor production from ASCs, making these cells a potential source for paracrine factors that can stimulate cartilage regeneration.
Highlights
Adult stem cell therapies such as adipose stem cells (ASCs) are an attractive option for various clinical applications because of their accessibility and ability to differentiate into multiple cell types[1]
Microencapsulation was able to increase the rate of all measured growth factor secretion in both GM and chondrogenic medium (CM) and the rates of IGF-I, TGF-β3 and VEGF-A secretions from all ASC cultures were significantly different compared to each other (Figure 1A, p
In CM, ASC microbeads secreted 27 fold more IGF-I, 1.9 fold more TGF-β3 and 3.7 fold more VEGF-A than what was retained within the microbead after 7 days
Summary
Adult stem cell therapies such as adipose stem cells (ASCs) are an attractive option for various clinical applications because of their accessibility and ability to differentiate into multiple cell types[1]. ASCs can be used for a variety of clinical applications, repairing cartilage focal lesions is an attractive option because of the tissue’s limited regenerative capacity and the lack of an effective treatment[7, 8]. Current cell therapies, such as autologous chondrocyte implantation aim to directly regenerate cartilage by providing a source of cells that can synthesize new tissue[9]. A new paradigm has emerged in using stem cells as growth factor production sources to stimulate diseased or damaged musculoskeletal tissues like cartilage to regenerate themselves[12, 13]
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