Mesenchymal Stem Cells for Cardiac Repair

Al-Khani, Abdullah Murhaf; Khalifa, Mohamed Abdelghafour; Haider, Khawaja Husnain

doi:10.1007/978-981-16-6016-0_11-1

Cited by 34 publications

(2 citation statements)

References 211 publications

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“…Consequently, stem cell preconditioning has been extensively employed for therapeutic purposes in clinical settings and has progressed to advanced phases of clinical trials[ 37 ]. Recent research has shed light on the role of ferroptosis as a form of regulated cell death in stem cell biology, focusing on CSE/H 2 S signaling due to its cardinal physiological and pathological roles in cell death.…”

Section: Introductionmentioning

confidence: 99%

Cellular preconditioning and mesenchymal stem cell ferroptosis

Zineldeen,

Mushtaq,

Haider

2024

World J Stem Cells

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In this editorial, we comment on the article published in the recent issue of the World Journal of Stem Cells . They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionine γ-lyase/hydrogen sulfide (H2S) pathway as a novel approach to treat vascular disorders, particularly pulmonary hypertension. Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh, unfavorable microenvironment of the injured tissue. They also secrete various paracrine factors against apoptosis, necrosis, and ferroptosis to enhance cell survival. Ferroptosis, a regulated form of cell death characterized by iron accumulation and oxidative stress, has been implicated in various pathologies encompassing degenerative disorders to cancer. The lipid peroxidation cascade initiates and sustains ferroptosis, generating many reactive oxygen species that attack and damage multiple cellular structures. Understanding these intertwined mechanisms provides significant insights into developing therapeutic modalities for ferroptosis-related diseases. This editorial primarily discusses stem cell preconditioning in modulating ferroptosis, focusing on the cystathionase gamma/H2S ferroptosis pathway. Ferroptosis presents a significant challenge in mesenchymal stem cell (MSC)-based therapies; hence, the emerging role of H2S/cystathionase gamma/H2S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention. Further research into understanding the precise mechanisms of H2S-mediated cytoprotection against ferroptosis is warranted to enhance the therapeutic potential of MSCs in clinical settings, particularly vascular disorders.

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Section: Introductionmentioning

confidence: 99%

Cellular preconditioning and mesenchymal stem cell ferroptosis

Zineldeen,

Mushtaq,

Haider

2024

World J Stem Cells

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“…Mesenchymal stem cells (MSCs) are emerging as a promising living bio-drug for treating HF patients[ 5 , 6 ]. Since the reporting of the first clinical study by Hamano et al [ 7 ] using autologous bone marrow-derived MSCs (BM-MSCs) as an adjunct to coronary artery bypass graft surgery in five patients, several clinical trials have established the safety of MSC-based therapy in cardiac and non-cardiac diseases[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

Jihwaprani,

Sula,

Charbat

et al. 2024

World J Cardiol

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BACKGROUND Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e. , stemness, viability, phenotypes, paracrine activity, etc. , need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention. AIM To investigate the effect of RoD of MSCs on safety and efficacy in HF patients. METHODS RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints. RESULTS Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001). CONCLUSION Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

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