Clinically relevant preservation conditions for mesenchymal stem/stromal cells derived from perinatal and adult tissue sources

Abstract

The interplay between mesenchymal stem/stromal cells (MSCs) and preservation conditions is critical to maintain the viability and functionality of these cells before administration. We observed that Ringer lactate (RL) maintained high viability of bone marrow–derived MSCs for up to 72 h at room temperature (18°C–22°C), whereas adipose‐derived and umbilical cord‐derived MSCs showed the highest viability for 72 h at a cold temperature (4°C–8°C). These cells maintained their adherence ability with an improved recovery rate and metabolic profiles (glycolysis and mitochondrial respiration) similar to those of freshly harvested cells. Growth factor and cytokine analyses revealed that the preserved cells released substantial amounts of leukaemia inhibitory factors (LIFs), hepatocyte growth factor (HGF) and vascular endothelial growth factor‐A (VEGF‐A), as well as multiple cytokines (eg IL‐4, IL‐6, IL‐8, MPC‐1 and TNF‐α). Our data provide the simplest clinically relevant preservation conditions that maintain the viability, stemness and functionality of MSCs from perinatal and adult tissue sources.

Stem cell-based therapy for human diseases

“…UC-MSCs are potential allogeneic cells for the treatment of cardiovascular disease, as they are “ready to use” and easy to isolate, they rapidly proliferate, and they secrete hepatocyte growth factors, 322 which are involved in cardioprotection and cardiovascular regeneration. 323 The pilot study using UC-MSCs in 30 patients with heart failure, called the RIMECARD trial, was the first reported trial for which the results supported the effectiveness of UC-MSCs, as seen in the improved ejection fraction, left ventricular function, functional status, and quality of life in patients administered UC-MSCs.…”

“…320 A 3-year follow-up report from the MyStromal-Cell Trial confirmed that patients who received AT-MSC administration maintained their preserved exercise capacity and their cardiac symptoms improved, whereas the control group experienced a significant reduction in exercise performance and a worsened cardiovascular condition. 321 UC-MSCs are potential allogeneic cells for the treatment of cardiovascular disease, as they are "ready to use" and easy to isolate, they rapidly proliferate, and they secrete hepatocyte growth factors, 322 which are involved in cardioprotection and cardiovascular regeneration. 323 The pilot study using UC-MSCs in 30 patients with heart failure, called the RIMECARD trial, was the first reported trial for which the results supported the effectiveness of UC-MSCs, as seen in the improved ejection fraction, left ventricular function, functional status, and quality of life in patients administered UC-MSCs.…”

“Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial”

“…The study showed that no serious adverse events or adverse events occurred in the patients. Women reported satisfaction with their sex lives; however, there was no significant change in AMH, FSH and estradiol levels (Nguyen T. et al, 2021).…”

“…Cells exhibit altered cellular functions leading to decreased regenerative bioactivity with increasing age (Peffers et al, 2016;Marędziak et al, 2016;Y.-H. K. Yang 2018). In addition, the authors have demonstrated that long-term type II diabetes mellitus could induce remarkable changes in mtDNA genetic profiles and negatively interfere with cell metabolism and bioactivity (Nguyen T. et al, 2021). On the other hand, potential genetic changes in the reproductive system need to be considered when allogenic cells are applied for the management of reproductive health (X.…”

“…ASCs signal to other cells through the synergistic action of soluble proteins and extracellular vesicles. ASCs are superior sources of growth factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), angiopoietin-1 and -2 (Ang-1 and Ang-2), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and insulin-like growth factor (IGF) ( Rehman et al, 2004 ; Sadat et al, 2007 ; Kingham et al, 2014 ; Dabrowski et al, 2017 ; Y.-H. An et al, 2021 ; Jiao et al, 2021 ; Ngo et al, 2021 ; Sumarwoto et al, 2021 ). These factors mediate ASCs to promote angiogenesis ( Jiao et al, 2021 ; Krawczenko and Klimczak 2022 ), cell survival ( Rehman et al, 2004 ), cell proliferation ( Jiao et al, 2021 ), and wound healing processes (Y.-H. An et al, 2021 ) in many disease models.…”