The exciting prospects of new therapies with mesenchymal stromal cells

Abstract

From the outset, it was apparent that developing new therapies with mesenchymal stem/stromal cells (MSCs) was not a simple or easy task. Among the earliest experiments was administration of MSCs from normal mice to transgenic mice that developed brittle bones because they expressed a mutated gene for type 1 collagen isolated from a patient with osteogenesis imperfecta. The results prompted a clinical trial of MSCs in patients with severe osteogenesis imperfecta. Subsequent work by large numbers of scientists and clinicians has established that, with minor exceptions, MSCs do not engraft or differentiate to a large extent in vivo. Instead the cells produce beneficial effects in a large number of animal models and some clinical trials by secreting paracrine factors and extracellular vesicles in a “hit and run” scenario. The field faces a number of challenges, but the results indicate that we are on the way to effective therapies for millions of patients who suffer from devastating diseases. This report was presented by the Author on receipt of the Career Achievement Award in Cell Therapy from the International Society for Cellular Therapy. Singapore, May 25, 2016.

Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats

“…36,37 Nanosized EVs enable communication between MSCs and immune cells and disseminate their parental components throughout the body via biological fluids. 38 Similar to MSCs, hUCMSC-derived EVs can home to rat nerve injuries as revealed by fluorescent imaging ( Figure 8). Although the precise molecular mechanisms through which MSC-EVs migrate into sites of injury remain incompletely defined, their high expression of migration-associated cytokines and chemokines 27,39 may account for their homing function.…”

Stem cell-based therapies in neonatology: a new hope

“…At the turn of this century, the observation that bone marrow-derived cells regenerate infarcted myocardium and that human MSCs differentiate to a cardiomyocyte phenotype in the adult murine heart, catapulted MSCs from niche cell to potent repair cell capable of regenerating damaged organs 2. Since, multiple laboratory studies have demonstrated the repair potential of MSCs in the heart, brain, lung, kidney, gut, skin, etc 3. In the neonatal lung, two proof of concept studies in mouse and rat pups exposed to high oxygen concentrations ignited excitement about the lung protective effect of MSCs and its clinical potential: a single intravenous or intratracheal administration of rodent bone marrow-derived MSCs improved survival and attenuated lung injury, inflammation and pulmonary hypertension spurring new hope in neonatology 4 5.…”

Mesenchymal Stem Cell Infusion Shows Promise for Combating Coronavirus (COVID-19)- Induced Pneumonia

“…MSCs have been employed extensively in cell therapy, which includes a plethora of preclinical research investigations as well as a significant number of clinical trials [10][11][12][13]. Safety and efficacy have been shown in many clinical trials.…”

“…The notable examples include the immune-mediated inflammatory diseases, such as graftversus-host disease and systemic lupus erythematosus [14][15]. Improved function after MSC infusions in multiple disease conditions has been mostly attributed to immunomodulatory effects, as these cells secrete a variety of paracrine factors, which interact with immune cells resulting eventually in immunomodulation [10][11][12][13]. The mechanisms underlying the improvements after MSC infusion in COVID-19 patients also appeared to be the robust antiinflammatory activity of MSCs.…”