Mesenchymal Stem Cells (MSCs) as living biodrugs have progressed to phase 3 clinical trials for cardiovascular applications. However, their limited ready-to-use availability hampers their routine clinical use, especially for emergency room use. This study aims to assess the potential effectiveness of cryopreserved MSCs (CryoMSCs) in RCTs for cardiac applications, offering a promising outlook for future treatments.

Our research was conducted with the utmost thoroughness and reliability. We comprehensively searched five databases, systematically reviewed all relevant RCTs, and evaluated the safety and efficacy of CryoMSCs in patients with heart disease. We primarily focused on the safety and effectiveness of CryoMSCs from various tissue sources. We also conducted a subgroup analysis based on post-thaw cell viability to determine treatment effects across different CryoMSCs viability statuses. Weighted Mean Differences (WMDs) and Odds Ratios were calculated to measure changes in the estimated treatment effects. All statistical analyses were performed using RevMan version 5.4.1 software, ensuring the thoroughness and reliability of our research. 

Seven RCTs with 285 patients were included. Short-term follow-up showed a 2.11% improvement in LVEF (WMD [95%CI]=2.11 [0.66, 3.56], P=0.004, I²=1%), with umbilical cord-derived MSCs being most effective. However, this was not sustained over 12 months, with no significant long-term effects. Subgroup analysis revealed a 3.44% improvement in LVEF (WMD [95%CI]=3.44 [1.46, 5.43], P=0.0007, I²=0%) for MSCs with viability over 80%. No significant differences were observed in major adverse cardiac events, 6-minute walking test, rehospitalization, or mortality compared to controls. 

In conclusion, CryoMSCs, with their significant short-term improvement in LVEF and minimal increase in major cardiac events, emerge as a promising treatment for heart failure. These findings support the potential of CryoMSCs in cardiovascular applications, reassure about their safety, and mitigate potential risks, offering hope for future treatments.

Moaz Safwan is a senior medical student at Sulaiman Alrajhi University in Saudi Arabia, aspiring to become an internist. He is skilled in conducting systematic reviews and meta-analyses, having worked on over ten projects in fields like stem cell-based therapy, cardiology, and oncology. Additionally, he has presented his projects at various conferences, including the 2023 Annual Saudi Heart Association Conference in Riyadh.