The therapeutic effect of secretome from human umbilical cord-derived mesenchymal stem cells in age-related osteoporosis

Abstract

Senile osteoporosis is closely related to the loss of function of stem cells. In this study, we tried to investigate the potential of secretome from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in recovering stem cell ability from senescence and then delaying bone loss. We first harvested bone marrow-derived mesenchymal stem cells (BMSCs) from young and old rats and then compared their cellular characteristics such as cell growth, anti-senescence and differentiation. The results showed that these abilities were negatively affected by animal aging. Subsequently, aged BMSCs were exposed to secretome from hUCMSCs, and we found that this loss of cell potential can be modified by secretome treatment. Thereafter, the secretome was loaded into silk fibroin-based hydrogels and used for an in vivo animal study. The results showed that compared to the old untreated group, the bone formation capacity of aged rats was improved by local treatment of secretome-loaded silk fibroin hydrogels. In conclusion, these findings demonstrated that secretome from hUCMSCs has the capacity to recover stem cell potential and delay local bone loss in age-related osteoporosis, which could potentially be applied in osteoporosis therapy in the future.

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…MSC‐CM reduced oxidative stress of aged bone marrow mesenchymal stromal cells (BMSCs) in vitro and reversed age‐related osteoporotic bone loss when delivered encapsulated in silk fibroin hydrogels. [ 51 ] MSC‐CM administered in a collagen sponge reduced inflammation (TNF‐α) and enhanced regeneration in a dose‐dependent manner in periodontal defects in rats [ 218 ] and in dogs, [ 64 ] while also promoting bone healing in rat calvaria defects. [ 80 ] Interestingly, bone regeneration by MSC‐CM delivered in an agarose gel was superior to that following transplantation of MSCs in the same carrier in calvaria defects.…”

A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

“…MSC-conditioned media (MSC-CM) which can be collected in vitro from MSC cultures contain cytokines, chemokines, and growth factors [230], as well as extracellular vesicles (EVs) [231]. It has been reported that MSC-secreted factors are conducive to the regeneration of bone defects, which may perhaps be attributed to the reduction of oxidative stress in aged BMSCs and the reverse of age-related bone loss [232]. Moreover, under hypoxia, the enhancement of MSC-CM-secreted factors can increase bone healing by simulation of endogenous MSCs [233].…”

Restoring aged stem cell functionality: Current progress and future directions

“…114 More recently, it was discovered that the secretome from umbilical cord-derived MSCs was able to induce differentiation and self-renewal of old MSCs. 115 The proliferation and differentiation capacity of passage 3 adult human synovium-derived MSCs (sMSCs) in different microenvironments were compared in vitro. 118 MSCs seeded onto a decellularized ECM secreted by fetal sMSCs greatly increased proliferation and differentiation capacity, chondrogenic potential, and expression of pluripotency markers compared to MSCs seeded on plastic or decellularized ECM secreted by adult sMSCs.…”

“…Indeed, the secretome of young MSCs has been shown to promote cardiac repair, 111 differentiation of NSCs into functioning glial cells and astrocytes, 112,113 and differentiation of MuSCs into functional muscle tissue 114 . More recently, it was discovered that the secretome from umbilical cord‐derived MSCs was able to induce differentiation and self‐renewal of old MSCs 115 …”