Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

Abstract

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.

The secretome of periodontal ligament stem cells from MS patients protects against EAE

“…We speculate that the beneficial effects produced by conditioned medium might be attributed to its EMVs fractions, adding further support in the context of personalized regenerative stem-cell free therapy for MS. Stem-cell free therapy approach has been emerged as potentially safer and cost-effective alternatives for a wide range of diseases57585960. Our preclinical data presented here suggest that secretome derived from hPDLSCs may represent a unique autologous therapeutic source in the clinical application of RR-MS patients.…”

The long-term fate of mesenchymal stem cells labeled with magnetic resonance imaging-visible polymersomes in cerebral ischemia

“…18,19 Initially, it was assumed that transdifferentiation of MSCs into neuronal and glial cells to replace damaged cells might play a pivotal role in stroke recovery. 18,20 Nonetheless, growing evidence suggested that the enhanced function recovery of MSCs might not be mainly associated with the transdifferentiation of MSCs. 20 Since MSCs can secrete a vast array of cytokines, chemokines, angiogenic factors, and growth factors, paracrine action might play an essential role in brain regeneration in MSCs therapy.…”

“…20 Since MSCs can secrete a vast array of cytokines, chemokines, angiogenic factors, and growth factors, paracrine action might play an essential role in brain regeneration in MSCs therapy. 19,20 Therefore, it needs further clarification whether it is with a definite single or integrated multiple mechanisms that MSCs function in stroke.…”

Multiple Sclerosis Under Attack; Shehata’s Therapy

“…MSCs have the unique ability to restore the deficits through the regenerative differentiation ability, in addition to the control and or prevention of the autoimmune and inflammatory condition. [50,51] Mesenchymal stem cells are very tolerated by the immune system, where they can attenuate the immunity through modulating T cell activation and proliferation, either by a direct cell-cell interaction or via soluble factors. In addition, this action is independent on the major histocompatibility (MHC) matching because MSCs are characterized by low expression level of MHC I and II, and lack the T cell costimulating molecules CD80 and CD86.…”

“…Moreover, MSCs secrete many immunomodulatory factors that include IL10, transforming growth factor β (TGFβ), prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF). [51,52] IL10 is one of the major anti-inflammatory cytokine that down regulates the expression of cytokines in the T helper-1 cells, as well as the major histocompatibility class-II antigens and costimulatory molecules on the surface of macrophages. Moreover, IL10 antagonizes the activity of NF-κB and is capable of suppressing the production of IL8 in a dose dependent manner.…”