Zhi Yong Chong, Chu Lin Tsai, Po Cheng Lin, Ming Hsi Chuang

¹Gwo Xi Stem Cell Applied Technology Co., Ltd., Hsinchu, Taiwan, ROC

*Corresponding author: genecold@gwoxi.com

GXNPC1^®, a novel autologous adipose-derived stem cell therapy for treating chronic stroke, focusing on angiogenesis, neural differentiation, and motor function improvement.

ABSTRACT

Gwo Xi Stem Cell Applied Technology Co., Ltd. (hereinafter “Gwo Xi”) is a Taiwan-based cell therapy company committed to developing stem cell medicines that address unmet medical needs. One of its key targets, chronic ischemic stroke, is among the most challenging neurological disorders, often leading to long-term disabilities and limited therapeutic options. Gwo Xi’s GXNPC1®, an autologous adipose-derived stem cell (ADSC) therapy, is designed to promote neurovascular repair, angiogenesis, and functional recovery, offering a promising regenerative approach for patients suffering from chronic ischemic stroke. Preclinical and IND clinical studies have demonstrated that GXNPC1^® exerts potent regenerative effects through angiogenesis, immunomodulation, and neuronal differentiation. Phase I and II trials conducted in Taiwan confirmed its safety profile and revealed consistent improvements in National Institutes of Health Stroke Scale (NIHSS). Through intracerebral administration, GXNPC1^® can directly target ischemic brain regions to enlarge infiltrated cells to take effect. GXNPC1^® is currently advancing toward Phase III clinical trial. With Taiwan’s recent enactment of the Regenerative Medicine Act (RMA) and the Regenerative Medicinal Products Act (RMPA) (collectively referred to as the “Regenerative Medicine Dual Legislation”), GXNPC1^® has completed Phase II clinical trials. The release of new laws will accelerate the commercialization of regenerative therapy products. GXNPC1® is expected to revolutionize the current treatment model for chronic ischemic stroke in Taiwan.

Keywords: Gwo Xi, stem cell, GXNPC1^®, chronic stroke, autologous, adipose, intracerebral injection, regenerative medicine.

INTRODUCTION

Chronic stroke remains one of the leading causes of long-term disability worldwide. Although thrombolysis and thrombectomy have revolutionized acute stroke management, their benefits are confined to a narrow therapeutic window (≦24 h), resulting in most patients progressing into the chronic stage with persistent motor, sensory, and cognitive impairments [1,2]. During this late phase, glial scarring, neuroinflammation, and synaptic disconnection severely restrict neuroplasticity and limit the capacity for functional and activity recovery. Consequently, there is an urgent need for therapeutic strategies that can actively promote neural regeneration, vascular remodeling, and reorganization of motor networks in chronic stroke patients.

Stem cell therapy has emerged as a promising approach to address these challenges [3,4,5]. Among various stem cell sources, adipose-derived mesenchymal stem cells (ADSCs) are particularly attractive due to their advantages, including ease of harvest, multilineage differentiation potential, and strong secretion of trophic and angiogenic factors [3,6]. GXNPC1^®, developed by Gwo Xi, is an autologous ADSC-based therapy designed to restore neurological function and coordination in patients with chronic stroke through proprietary cell culture technology.

This article reviews the preclinical evidence, clinical outcomes, and mechanistic rationale of GXNPC1^®, highlighting its therapeutic innovation in chronic stroke rehabilitation and its ongoing development toward Phase III clinical trial under RMPA in Taiwan.

PRECLINICAL BASIS AND EXPERIMENTAL EVIDENCE

GXNPC1^® utilizes autologous adipose-derived stem cells (ADSCs) harvested from 3-5 grams of each patients’ adipose tissue and processed under Good Manufacturing Practice (GMP) standards to ensure quality, sterility, and reproducibility. Extensive preclinical studies have demonstrated the therapeutic potential of ADSCs in chronic ischemic stroke models. In thromboembolic stroke models, ADSC transplantation significantly enhanced post-stroke behavioral recovery and mitigated cortical neuronal apoptosis, indicating neuroprotective and restorative effects [7,9].

Importantly, these studies confirmed a favorable safety profile, with no evidence of tumorigenicity or abnormal cell proliferation. The functional gains observed in animal models were sustained over several weeks to months, indicating durable benefits beyond transient trophic effects.

These preclinical data provided the foundational evidence for the clinical translation of GXNPC1^®, supporting its capacity to enhance recovery in chronic stroke by improving local perfusion and promoting tissue remodeling. The results also validated the feasibility of intracerebral injection as a route of administration (ROA).

CLINICAL TRANSLATION AND TRIAL EVIDENCE

The first-in-human Phase I trial (NCT02813512) was conducted in Taiwan by Dr. Lin, Shinn-Zong, involving three chronic stroke patients with stable deficits persisting for over six months. Each participant received a intracerebral injection of 1×10⁸ autologous ADSCs within 1 mL. The procedure was well tolerated, with no severe adverse events or suspected unexpected serious adverse reactions (SUSARs) observed during six months of follow-up. MRI scans showed localized signal alterations near the tranplantation tract, indicating tissue remodeling or possible graft survival. Functionally, participants improved by 5–15 points on the National Institute of Health Stroke Scale (NIHSS), 25–50 points on the Barthel Index, and up to 21 points on the Berg Balance Scale [8]. These improvements suggest meaningful recovery in a population typically resistant to spontaneous improvement.

Subsequently, Phase II (NCT04088149) study expanded patient enrollment, with data showing continued safety and measurable clinical benefits. The high-dose cohort achieved an average NIHSS improvement of 2.7 points by 24 weeks, and 89% of participants exhibited improved behavioral and functional metrics. Currently, GXNPC1^® has applied for Phase III clinical trials and, under Taiwan Regenerative Medicinal Products Act, has the potential to receive a 5-year conditional approval to be marketed in advance.

THERAPEUTIC ADMINISTRATION AND PRECISION ADMINISTRATION

A defining feature of GXNPC1^® lies in its precise administration. Unlike intravenous or intrathecal stem cell infusions, GXNPC1^® is administered directly into the brain via stereotactic guidance. This approach ensures localized cell distribution within peri-infarct regions, maximizing regenerative impact while minimizing systemic exposure. Such precision administration represents a major advancement in cell-based therapeutics, aligning with the principles of personalized medicine and targeted neurosurgical delivery.

COMPARATIVE ADVANTAGES AND INNOVATION

GXNPC1^® distinguishes itself through several technological and clinical advantages: (1) It is an autologous, patient-specific therapy with minimal immunogenic risk; (2) It leverages a well-established ADSC processes, providing qualified cell dosage under GMP standards; (3) Its paracrine and exosomal signaling provide multi-dimensional repair; and (4) It has achieved advanced clinical development, with a Phase III application underway. The therapy has been recognized with innovation awards from Taiwan’s healthcare and biotech agencies, reflecting confidence in its translational and commercial potential.

CHALLENGES AND FUTURE PERSPECTIVES

Despite the promising clinical outcomes observed with GXNPC1^®, several challenges must be addressed to enable its routine application for chronic stroke rehabilitation. Firstly, autologous cell therapy requires individualized manufacturing. The overall cycle is complex and involves multiple stages. This limits scalability. Gwo Xi’s strategy is to simplify the treatment process through modular processes: for example, introducing standardized cell cryopreservation and In-Process Control (IPC) to shorten turnaround time, reduce patient waiting times and reduce center pressure.

Meanwhile, optimizing administration strategies, such as cell dosage escalation, and timing relative to stroke onset, will be critical to enhance efficacy [10]. Establishing solid clinical biomarkers to monitor response, along with standardized functional assessment scales, will facilitate individualized treatment planning. Moreover, integration of advanced imaging techniques, including MRI-based perfusion mapping and diffusion tensor imaging, can provide objective evidence of structural and functional improvement in neural circuits.

Finally, expanding the manufacturing and quality control framework for ADSC processes fitting GMP standards will be essential to ensure consistent product quality. Addressing these translational and operational challenges will be pivotal for GXNPC1^® to achieve broad clinical adoption and fulfill its potential as a promising stem cell therapy for patients with chronic stroke.

CONCLUSION

GXNPC1^® represents a scientifically grounded and clinically validated regenerative therapy that integrates angiogenesis, neurogenesis, and immunomodulation to address chronic ischemic stroke. Its strong safety record, measurable functional benefits, and advancement to Phase III trials mark it as a frontrunner in the field of regenerative neurology. By combining precision delivery with the intrinsic repair capabilities of ADSCs, Gwo Xi’s GXNPC1^® offers renewed hope for patients facing long-term disability after stroke and sets a benchmark for future neurodegenerative therapies.

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