Recent clinical trials with stem cells to slow or reverse normal aging processes

Abstract

Aging is associated with a decline in the regenerative potential of stem cells. In recent years, several clinical trials have been launched in order to evaluate the efficacy of mesenchymal stem cell interventions to slow or reverse normal aging processes (aging conditions). Information concerning those clinical trials was extracted from national and international databases (United States, EU, China, Japan, and World Health Organization). Mesenchymal stem cell preparations were in development for two main aging conditions: physical frailty and facial skin aging. With regard to physical frailty, positive results have been obtained in phase II studies with intravenous Lomecel-B (an allogeneic bone marrow stem cell preparation), and a phase I/II study with an allogeneic preparation of umbilical cord-derived stem cells was recently completed. With regard to facial skin aging, positive results have been obtained with an autologous preparation of adipose-derived stem cells. A further sixteen clinical trials for physical frailty and facial skin aging are currently underway. Reducing physical frailty with intravenous mesenchymal stem cell administration can increase healthy life expectancy and decrease costs to the public health system. However, intravenous administration runs the risk of entrapment of the stem cells in the lungs (and could raise safety concerns). In addition to aesthetic purposes, clinical research on facial skin aging allows direct evaluation of tissue regeneration using sophisticated and precise methods. Therefore, research on both conditions is complementary, which facilitates a global vision.

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

“…Twenty years ago, the National Institute on Aging (NIA, USA) launched an Intervention Testing Program (ITP) dedicated to identifying longevity candidates in a genetically heterogeneous mouse model (candidates are evaluated in three independent laboratories) [22]. The ITP has identified two longevity drug candidates, the immunosuppressant rapamycin [23] and the antidiabetic acarbose [24] that are currently under clinical investigation [3]. Vitamin D and the antidiabetic drug metformin have been identified in other animal models and are also under clinical investigation [3,25].…”

“…The ITP has identified two longevity drug candidates, the immunosuppressant rapamycin [23] and the antidiabetic acarbose [24] that are currently under clinical investigation [3]. Vitamin D and the antidiabetic drug metformin have been identified in other animal models and are also under clinical investigation [3,25].…”

“…All-cause mortality is a marker of longevity [3]. The above results from observational studies suggest that vitamin D supplementation [in persons with low 25(OH)D serum levels] [34,36] as well as metformin [40] can significantly reduce all-cause mortality and prolong life expectancy (Table 1).…”

“…It is interesting to mention that two other longevity candidates (rapamycin and acarbose) are currently in clinical trials, but the results have not yet been reported to ClinicalTrials.gov [3].…”

“…A substantial effort is currently deployed to find specific drugs and biologics intended to slow or reverse normal aging processes. Currently, several literature reviews are available that identify and analyze clinical studies with the following specific families of compounds (Table 1): (i) longevity candidates [2,3], (ii) mesenchymal stem cells [4][5][6], (iii) senolytics drugs [7][8][9], (iv) sirtuin activators [10][11][12][13], and (v) nicotinamide adenine dinucleotide (NAD) + precursors [14][15][16][17][18]. An overview of emerging results and future perspectives from clinical studies conducted with the five compound families mentioned above is presented here.…”