Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors. Adv Drug Deliv Rev

Department of Internal Medicine, University of California, Davis, Sacramento, 95817, USA.
Advanced drug delivery reviews (Impact Factor: 15.04). 10/2010; 62(12):1167-74. DOI: 10.1016/j.addr.2010.09.013
Source: PubMed


Mesenchymal stem cells (MSC) are a promising tool for cell therapy, either through direct contribution to the repair of bone, tendon and cartilage or as an adjunct therapy through protein production and immune mediation. They are an attractive vehicle for cellular therapies due to a variety of cell intrinsic and environmentally responsive properties. Following transplantation, MSC are capable of systemic migration, are not prone to tumor formation, and appear to tolerize the immune response across donor mismatch. These attributes combine to allow MSC to reside in many different tissue types without disrupting the local microenvironment and, in some cases, responding to the local environment with appropriate protein secretion. We describe work done by our group and others in using human MSC for the sustained in vivo production of supraphysiological levels of cytokines for the support of cotransplanted hematopoietic stem cells and enzymes that are deficient in animal models of lysosomal storage disorders such as MPSVII. In addition, the use of MSC engineered to secrete protein products has been reviewed in several fields of tissue injury repair, including but not limited to revascularization after myocardial infarction, regeneration of intervertebral disc defects and spine therapy, repair of stroke, therapy for epilepsy, skeletal tissue repair, chondrogenesis/knee and joint repair, and neurodegenerative diseases. Genetically engineered MSC have thus proven safe and efficacious in numerous animal models of disease modification and tissue repair and are poised to be tested in human clinical trials. The potential for these interesting cells to secrete endogenous or transgene products in a sustained and long-term manner is highly promising and is discussed in the current review.

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Available from: Jan A Nolta, Jul 03, 2015
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    • "Truly, it has been shown that transplantation of GM-MSCs which is expressing therapeutic growth factors generates new bone and cartilage formation much faster than exogenous treatment of growth factors (Lee et al. 2010). Thus, mesenchymal stem cells (MSCs) have received a great deal of attention as a delivery vehicle of growth factors following gene modification (Kofron and Laurencin 2006, Meyerrose et al. 2010, Porada and Almeida-Porada 2010, Qi et al. 2012) because they show sustained release of therapeutic growth factors as well as differentiation toward tissue specific cells at the same time. Therefore, these synergistic effects are able to distinctly enhance bone and cartilage tissue compared with individual treatment of MSCs and growth factors. "

    Full-text · Article · Sep 2014
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    • "MSCs have strong anti-inflammatory and immunosuppressive activity, rendering them very attractive for successful autologous, as well as heterologous, transplantations without requiring pharmacological immunosuppression [57, 58]. They do not give uncontrollable growth or tumour formation [59]. There is no need of genetic modification or pretreatment before transplantation; since MSCs are able to express in vivo immunosuppressive factors, immune rejection problems are overcame [60, 61]. "
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    • "Genetically modified stem cells have been proposed as a promising tool for cell therapy. They have been proven safe and effective in tissue repair or disease treatment by numerous animal tests and are now ready for human clinical trials.39 Our present data, together with those previously reported,9 support the notion that genetically engineered adipose stem cells with GDF5 might be applied for cartilage regeneration. "
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