Mesenchymal Stromal Cell Characteristics and Regenerative Potential in Cardiovascular Disease

Abstract

Administration of mesenchymal stromal cells (MSCs) is a promising strategy to treat cardiovascular disease (CVD). As progenitor cells may be negatively affected by both age and comorbidity, characterization of MSC function is important to guide decisions regarding use of allogeneic or autologous cells. Definitive answers on which factors affect MSC function can also aid in selecting which MSC donors would yield the most therapeutically efficacious MSCs. Here we provide a narrative review of MSC function in CVD based on a systematic search. A total of 41 studies examining CVD-related MSC (dys)function were identified. These data show that MSC characteristics and regenerative potential are often affected by CVD. However, studies presented conflicting results, and directed assessment of MSC parameters relevant to regenerative medicine applications was lacking in many studies. The predictive ability of in vitro assays for in vivo efficacy was rarely assessed. There was no correlation between quality of study reporting and study findings. Age mismatch was also not associated with study findings or effect size. Future research should focus on assays that assess regenerative potential in MSCs and parameters that relate to clinical success.

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

“…Aging is the main driver of CVD progression, inducing vascular changes and reducing regenerative potential of stem cells. In turn, CVDs also affect the progenitor cell compartment, causing increased senescence, reduced proliferation, and regenerative potential in MSCs . This could represent a limitation for autologous cell therapy in CVDs, which may be solved by using allogeneic MSCs, selected on the basis of age and comorbidities.…”

Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

“…Preclinical studies show a pronounced reduction in vascular regenerative effects of BM mononuclear cells of donors with cardiovascular disease (CVD), including CKD [16]. In culture-expanded MSCs, the effect of CVD is less clear, with conflicting reports depending on the cardiovascular disease (model) and little information available for CKD [17]. MSC immunomodulatory properties seem preserved in BM MSCs, though it is currently unknown whether CKD negatively influences the paracrine regenerative potential of BM MSCs and BM MSCderived EV [17][18][19].…”

“…Stem Cells International diseases have been shown to affect the stem cell niche, potentially reducing the effectiveness of patient-derived progenitor cells [28]. MSCs have been shown to be less affected by this than other cell types considered for cell therapy, but whether disease-related dysfunction carries over in the cell product seems to depend on the disease [17].…”

“…Furthermore, in vitro studies have shown that a uremic environment negatively affects progenitor cell function [37,38]. While cell dysfunction might be resolved through ex vivo culture, in many cardiovascular diseases, MSC dysfunction remains present [17]. Studies on MSCs from CKD patients yielded conflicting results; Yamanaka and colleagues showed that adipose tissue-(AT-) derived MSC displayed reduced proangiogenic effects after implantation of MSC in vivo [39], contrasted by studies by Reinders and colleagues that showed that CKD and healthy MSCs derived from AT and BM produce similar amounts of cytokines essential for the proangiogenic properties of MSCs in vitro [18,19].…”

Advanced glycation end products and adipocytokines and oxidative stress in placental tissues of pregnant women with gestational diabetes mellitus

“…The AGEs-RAGE signaling pathway, formed by advanced glycation end product receptor (RAGE) and its ligands, advanced glycation end products (AGEs), is closely related to the occurrence and development of glucose metabolism disorders, and can activate inflammatory reactions and oxidative stress (7). The AGEs accumulation caused by persistent hyperglycemia during gestation is one of the main factors leading to abnormal fetal development (8). Visfatin, a newly discovered adipocytokine, is mainly secreted by visceral fat cells and is related to insulin secretion, glucose uptake and abnormal glucose tolerance (9).…”