Fight Aging!

Research is ever slower than we would all like it to be, but the foundations of the next generation of stem cell therapies are being assembled at a comparatively rapid pace, thanks to a large and increasing level of funding and support. While it remains the case that as a society we collectively place a very low priority on medical research and development in comparison to the benefits it is capable of delivering, regenerative medicine based on the use and manipulation of stem cells is one of the most active fields within that constraint, rivaling the cancer research edifice. Would that the world wakes up as this age of biotechnology continues, realizing that health and longevity can be purchased at a falling price in time and money, and ever more people vote with their purses for research and medicine over circuses and war. One can hope.

Here is a selection of recent stem cell research, representative of the sort of work taking place in the field. Not a week goes by without the publication of an incremental advance that would have captured the headlines a decade ago, but is now just a matter of course. We'll be making the same comparisons ten years from now, looking back at today's grand advances, made small by progress.

Stem cells could help mend a broken heart, but they've got to mature

Currently, the only treatment options for damaged heart muscle are surgery, if possible, and for the worst cases, a whole heart transplantation. But there's a huge shortage of organs for transplantation, and for this reason, we need to find new strategies to treat heart disease. Stem cells have great potential to fill this void. They're a unique type of cell that starts out unspecialized but can multiply and turn into specialized cells of the adult body - for instance, brain cells or heart muscle cells, officially called cardiomyocytes.

This relies upon turning stem cells into heart muscle cells - but even once they differentiate, the heart cells remain immature. They're not fully developed, having characteristics you'd find in a fetus, not an adult. To advance these possible therapies, we need ways to take these heart muscle cells one step further, to maturity. I'm studying how the heart's natural environment affects that maturation process. I focus on how the extracellular matrix, or scaffold, of the heart affects maturation. The overall goal is to find a way to create from stem cells fully functioning, mature heart cells that can be safely and effectively used for transplantation therapies and drug screening applications.

Filling a void in stem cell therapy

Stem cell therapies have potential for repairing many tissues and bones, or even for replacing organs. Tissue-specific stem cells can now be generated in the laboratory. However, no matter how well they grow in the lab, stem cells must survive and function properly after transplantation. Getting them to do so has been a major challenge for researchers. Possible stem cell therapies often are limited by low survival of transplanted stem cells and the lack of precise control over their differentiation into the cell types needed to repair or replace injured tissues. A team has now developed a strategy that has experimentally improved bone repair by boosting the survival rate of transplanted stem cells and influencing their cell differentiation. The method embeds stem cells into porous, transplantable hydrogels.

Poststroke Cell Therapy of the Aged Brain

The efficacy of stem cell therapies for stroke so far is discouragingly low mainly because the time course of interactions between host neuroinflammatory response, the main obstacle to exogenous-mediated neuronal precursor cells, and exogenously administered stem cells is still unknown. Although mesenchymal stem cell transplantation into the brain has ascribed beneficial effects in preclinical studies of neurodegenerative or neuroinflammatory disorders, only some studies reported that stem cells can survive in a strong neuroinflammatory environment such as an ischemic area in stroke.

To conclude, these findings strongly suggest that UCB derived cells have significant neurogenic potential but this potential has to be used in a more efficient manner to treat neurological diseases like stroke in aged people. Antineuroinflammatory therapies are a potential target to promote regeneration and repair in diverse injury and neurodegenerative conditions by stem cell therapy. Therefore, the challenge now is to determine in detail the cross talk between different populations of immune cells and grafted neural stem progenitor cells at different phases after stroke in aged brain.

Mesenchymal stem cell therapy for osteoarthritis: current perspectives

Osteoarthritis is a prevalent chronic degenerative joint disease that will continue to impose an increasing burden on the aging population unless disease-modifying therapies are developed. The current standard of care with risk factor modification, pain management, and joint replacement will be inadequate to meet the needs of society moving forward. Mesenchymal stem cells (MSCs) offer a potential regenerative solution given their ability to differentiate to all tissues within a joint and modulate the local inflammatory response. Although these characteristics suggest they provide ideal building blocks to restore damaged joints, a strong body of evidence supports MSC-guided regeneration through paracrine stimulation of native tissue.

Further preclinical work will be mandatory to establish the mechanism by which MSCs have demonstrated a proof-of-concept to heal osteoarthritic lesions as this will have critical implications for clinical implementation strategies. Determining the ideal MSC source, processing, and delivery vehicle are further challenges that must be addressed to optimize biologics-based treatment of osteoarthritis. In 2015, the translation of MSCs to clinical therapy for osteoarthritis has been slow; however, signs of progress are evident and ongoing trials may show efficacy to indicate these products can serve as the disease-modifying therapy necessary to stem the tide of osteoarthritis.

Ex Vivo Expansion and In Vivo Self-Renewal of Human Muscle Stem Cells

In adult mammals, skeletal muscle is regenerated by a population of tissue-resident muscle stem cells, also known as satellite cells. Quiescent satellite cells in uninjured muscle are activated in response to injury or disease. Owing to a limited understanding of human satellite cell biology, it is still unclear as to what extent findings from mouse studies will translate to human cell-based therapies. A major barrier to the development of stem cell-based therapies is the inability to generate large numbers of transplantable stem cells with the potential to both self-renew and differentiate. In general, the contribution of donor satellite cells to muscle regeneration has been shown to correlate with the number of cells transplanted.

To further our understanding of human satellite biology, we used prospective cell isolation, RNA sequencing (RNA-seq) analyses, and cell transplantation to study a defined population of human myogenic progenitors with the potential to self-renew. This information was leveraged to identify changes in the molecular phenotype and self-renewal potential within the purified satellite cell population. Specifically, we mapped a core transcription factor regulatory network of self-renewal, and we established an essential role for p38 mitogen-activated protein kinase (MAPK) in the regulation of human satellite cell regenerative capacity akin to that observed in the mouse. Reversible pharmacologic inhibition of p38 in cultured human satellite cells resulted in a gene expression program consistent with the promotion of self-renewal, and it allowed for expansion of a population of satellite cells ex vivo with enhanced self-renewal and engraftment potential.