Safety and Tolerability Study of Mesenchymal Stem Cells, HeXell-2020, in Elderly Subjects With Mild to Moderate Frailty Syndrome

Frailty Syndrome (FS) is a complex clinical phenotype characterized by increased vulnerability and reduced physiological reserve resulting from progressive decline across multiple physiological systems. Clinically, FS is manifested by reduced grip strength, exhaustion, slower walking speed, low physical activity, and unintentional weight loss. This condition is associated with elevated oxidative stress, chronic inflammation, decreased muscle mass, and organ dysfunction, which collectively contribute to an increased risk of disability, hospitalization, and mortality.

The pharmacological efficacy of MSCs has been extensively investigated including the secretion of immunomodulatory molecules, antioxidative enzymes, pro-angiogenic growth factors, and anti-apoptotic agents that collectively target multiple pathological mechanisms underlying frailty syndrome. UC-MSCs also exert potent anti-apoptotic effects by upregulating the expression of anti-apoptotic protein and simultaneously downregulating cellular senescence and apoptosis.

The investigational Drug Product (DP), HeXell-2020, consists of allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) isolated from human Wharton's jelly, which is intended to treat patients with FS. A GLP-compliant eleven repeated-dose (once every 7 days) toxicity study (Study Number 21005IV01), in which three does levels (1.5 × 10e6, 1.5 × 10⁷, 7.5 × 10⁷ cells/kg/dose) of HeXell-2020 or vehicle control was administered to NOD/SCID mice, was conducted to evaluate toxicity, local tolerance, and biodistribution. During the observation period, most of the survived animals appeared normal in all control and treated groups after dosing. The MTD (maximum tolerated dose) of HeXell-2020 is determined to be 1.5 × 10⁷ cells/kg/dose for 11 doses.

In current in vivo studies, rodents were administered UC-MSCs, which effectively restored skeletal muscle function by modulating extracellular matrix composition, activating muscle satellite cells, promoting autophagy, and mitigating cellular senescence through down-regulation of intracellular senescence signaling pathways. These mechanisms led to improved muscle mass, strength, and physical performance, directly addressing core symptoms of frailty. MSCs were observed to promote angiogenesis and improve tissue perfusion by secreting angiogenic factors, thereby facilitating capillary network formation and accelerating tissue regeneration.

This is a Phase I, open-label, dose-escalation study designed to evaluate the safety and tolerability of HeXell-2020 in elderly subjects with mild to moderate FS. Subjects aged 60 to 85 years will be enrolled. Up to 12 subjects will be sequentially allocated, and the study will follow a standard "3+3" dose-escalation design to determine the Maximum Feasible Dose (MFD). This study is designed to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) product HeXell-2020 intravenous infusion in frail adults prior to further clinical development.