At least one group is running trials of stem cell transplants as a potential treatment for age-related frailty syndrome: the scope of the possible in the near term is to find way to incrementally improve the condition, not produce a sizable reversal, but that is an improvement over the current situation, given that there is no effective treatment. The closest thing to a standardized, proven, reliable class of stem cell therapies involves the use of mesenchymal stem cells, sourced from a patient, or from lines of cells grown and engineered for transplantation with minimal risk. The primary outcome of mesenchymal stem cell therapies, or at least the reliable outcome, is a reduction in the systemic, chronic inflammation that accompanies old age. While it is entirely possible that other mechanisms are at work, the cells typically don't last long following transplantation, and thus it is the brief signaling changes that must produce benefits that can last for months or longer.

Chronic inflammation is a major problem in aging. It drives progression of most of the age-related conditions, and high levels of inflammation are certainly considered to be a major component of frailty syndrome in the old. In the context of a general treatment for frailty based on reductions in inflammation, the focus is less on the acceleration of specific age-related conditions over time, however, and more on the immediate consequences of constant high levels of inflammation for cell biochemistry, pain, cognitive function, joint function, regeneration, and tissue maintenance. Many aspects of age-related dysfunction are to some degree being actively maintained in their current impacted state by the presence of inflammation - take away that inflammation, and the problems subside a little, back to the lower level of harm and loss expected due to accumulated cell and tissue damage.

In recent years, it has become clear that chronic inflammation, as opposed to the normal short-term inflammation resulting from injury or infection, disrupts the finely tuned dance carried out between tissue and immune system needed for regeneration. This is an emerging theme in the investigation of how senescent cells cause aging, for example, as these unwanted cells are potent sources of inflammatory signaling. So if we see unreliable or marginal benefits from stem cell therapies that look like enhanced regeneration, it might well be that this is at root a short-term reduction in the age-related disruption of tissue maintenance - perhaps enough to allow a little reconstruction to take place in some patients. This is speculation, of course, and the cellular biochemistry is challenging to investigate; we should probably expect a first generation of moderately reliable therapies in advance of complete understanding of their mechanisms. Here is another point to consider on this topic: if the inflammation model of benefits is correct, then clearance of senescent cells should be at least as good a treatment for frailty as mesenchymal stem cell transplant, and probably better and more lasting.

Stem Cell Transplantation for Frailty

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty

The purpose of this Phase 1 pilot study, AllogeneiC Human Mesenchymal Stem Cell in Patients with Aging FRailTy via IntravenoUS Delivery (CRATUS), was to evaluate the safety and tolerability of allogeneic hMSCs (allo-hMSCs) in patients with aging frailty and to explore domains of treatment efficacy of allo-hMSCs through the reduction of signs and symptoms of aging frailty. The major new findings of CRATUS are that intravenous allo-hMSC infusions are safe and well tolerated in elderly individuals with early signs and symptoms of frailty. Importantly, there were improvements in a constellation of parameters that are important predictors of morbidity and mortality in patients with aging frailty. With no current standard of care for frailty, allo-hMSCs may hold great promise as a cell therapy agent for patients with this syndrome. The underlying basis for positive effects of allo-MSCs are likely due, at least in part, to anti-inflammatory and proregenerative effects. In this regard, frailty is characterized by systemic inflammation and low "reserve capacity" of organ systems thought due to diminished endogenous stem cell production. Replenishment of the body's stem cell "factory" and/or revitalization of stem cell niches via intravenous infusion of allo-hMSCs may help treat the morbidities associated with aging frailty.

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial