Concise Review: Optimizing Expansion of Bone Marrow Mesenchymal Stem/Stromal Cells for Clinical Applications

Abstract

Bone marrow-derived mesenchymal stem/stromal cells (MSCs) have demonstrated success in the clinical treatment of hematopoietic pathologies and cardiovascular disease and are the focus of treating other diseases of the musculoskeletal, digestive, integumentary, and nervous systems. However, during the requisite two-dimensional (2D) expansion to achieve a clinically relevant number of cells, MSCs exhibit profound degeneration in progenitor potency. Proliferation, multilineage potential, and colony-forming efficiency are fundamental progenitor properties that are abrogated by extensive monolayer culture. To harness the robust therapeutic potential of MSCs, a consistent, rapid, and minimally detrimental expansion method is necessary. Alternative expansion efforts have exhibited promise in the ability to preserve MSC progenitor potency better than the 2D paradigm by mimicking features of the native bone marrow niche. MSCs have been successfully expanded when stimulated by growth factors, under reduced oxygen tension, and in three-dimensional bioreactors. MSC therapeutic value can be optimized for clinical applications by combining system inputs to tailor culture parameters for recapitulating the niche with probes that nondestructively monitor progenitor potency. The purpose of this review is to explore how modulations in the 2D paradigm affect MSC progenitor properties and to highlight recent efforts in alternative expansion techniques.

Bone marrow mononuclear cells enhance anti-inflammatory effects of pravastatin against isoproterenol-induced myocardial infarction in rats

“…The present data clearly showed a significant increase in cardiac TNF and IL-1 in the ISO only-treated rats. This finding agrees with that of Hoch and Leach (2015), who demonstrated marked elevations of various inflammatory mediators (as interleukins and TNF) in cases of AMI and congestive heart failure. The source of TNF following the myocardial ischemia is mainly from cardiac mast cell degranulation (Frangogiannis et al 2002).…”

Bone Morphogenetic Protein‐2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels

“…MSCs are under broad investigation for their potential to promote bone healing. [30, 31] Furthermore, BMP-2 is the active ingredient of at least one commercial product that promotes bone formation by delivering high dosages of BMP-2 from a collagen sponge. [32] BMP-2 has been reported to induce apoptosis in numerous cell types in culture, including osteoblasts and MSCs, [17–19] potentially impeding the success of cell-based therapies for bone healing.…”

Should hypoxia preconditioning become the standardized procedure for bone marrow MSCs preparation for clinical use?

“…Improved experimental outcomes have been observed in the treatment of some diseases in animals by hypoxia-cultured MSCs compared with those cultured in normoxia [4,7]; but according to the database of clinicaltrials.gov, this procedure has been considered only in a handful of clinical studies, such as pulmonary emphysema (NCT01849159) and ischemic limb disease (NCT02336646), in the attempt to (re-) educate cells to survive in an oxygen-deprived environment/tissue. There are a number of possible reasons that may explain this phenomenon.…”