Mesenchymal stem cells-derived therapies for subarachnoid hemorrhage in preclinical rodent models: a meta-analysis

Abstract

Background Mesenchymal stem cells (MSCs) and MSCs-derived extracellular vesicles (EVs) have emerged as potential novel therapies for subarachnoid hemorrhage (SAH). However, their effects remain incompletely understood. We aim to comprehensively evaluate the effect of MSCs-derived therapies in rodent models of SAH. Methods We searched PubMed, EMBASE, and Web of Science up to September 2021 to identify studies that reported the effects of MSCs or MSCs-derived EVs in a rodent SAH model. Neurobehavioral score was extracted as the functional outcome, and brain water content was measured as the histopathological outcome. A random-effects model was used to calculate the standardized mean difference (SMD) and confidence interval (CI). Results Nine studies published from 2018 to 2021 met the inclusion criteria. Studies quality scores ranged from 5 to 10, with a mean value of 7.22. Our results revealed an overall positive effect of MSCs and MSCs-derived EVs on the neurobehavioral score with a SMD of − 2.21 (95% CI − 3.14, − 1.08; p < 0.0001). Meanwhile, we also found that MSCs and MSCs-derived EVs reduced brain water content by a SMD of − 2.09 (95% CI − 2.99, − 1.19; p < 0.00001). Significant heterogeneity among studies was observed, further stratified and sensitivity analyses did not identify the source of heterogeneity. Conclusions Our results suggested that MSCs-derived therapies prominently improved functional recovery and reduced brain edema in the rodent models of SAH. Notably, the limitations of small sample size should be considered when interpreting the results, and large animal studies and human trials are needed for further investigation.

Exosomes in Vascular/Neurological Disorders and the Road Ahead

“…Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapeutic approach for subarachnoid hemorrhage (SAH) in rodent models [178]. The therapeutic potential of MSCs in SAH was demonstrated by the intravenous administration of MSCs improving structural integrity and promoting functional recovery in rats subjected to SAH [179][180][181].…”

“…The therapeutic potential of MSCs in SAH was demonstrated by the intravenous administration of MSCs improving structural integrity and promoting functional recovery in rats subjected to SAH [179][180][181]. A study demonstrated that administering bone marrow MSC (BMSC) alle-viated early brain injury (EBI) induced by SAH and reduced neurobehavioral impairments, partly through inhibiting microglia activation [178].…”

Global scientific trends on exosomes therapy for osteoporosis from 2004 to 2023: A bibliometric and visualized analysis

“…MSCs isolated from adult tissues have a broad capacity to proliferate and differentiate into various cell lineages. [39] In recent years, the therapeutic mechanism of MSCs in tissue repair has shifted from one based on cell differentiation and replacement to one based on cell secretion and paracrine signaling. [40] Among the wide range of nutritional factors, MSC-derived exosomes have therapeutic effects in multiple injury or disease indications, including bone defects and OP.…”

Neuroinflammation and subarachnoid hemorrhage: a revised look at the literature

“…Non-aneurysmal SAH models are mainly created via two methods: (1) prechiasmatic and cisterna magna blood injection models or (2) endovascular perforation [ 108 ]. These models are widely used, as evidenced by a recent study that used them to test mesenchymal stem cells-derived therapies for SAH as well [ 111 ].…”