Trang Thao Quoc Pham, MD, Ph.D
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan
Dept. of Dermatology, Faculty of Medicine, University of Medicine & Pharmacy, Ho Chi Minh City, Vietnam

Introduction

In recent years, cell and gene therapy (CGT) has experienced remarkable growth in Vietnam, mirroring global innovation while leveraging local scientific expertise. CGT in Vietnam has transitioned from early experimental efforts to a more structured and translational phase, marked by increasing clinical application, technological refinement, and national-level strategic direction. Since the mid-1990s, Vietnam has achieved significant milestones, such as its first hematopoietic stem cell transplantation (HSCT) for children with Wiskott-Aldrich syndrome (WAS) [1], especially those derived from adipose tissue, has expanded rapidly, with clinical trials demonstrating their safety and efficacy in treating aging-related low-grade inflammation, cartilage injury, and psoriasis-like inflammation [2-4]. Next‑generation approaches under investigation encompass MSC‑derived exosomes for treating photoaging and promoting wound repair [5, 6], as well as protocols to enrich Muse cells from umbilical cord–derived mesenchymal stem cells (MSCs) [7]. Notably, the country’s transition from pioneering research to the development of national strategies and standardized clinical applications. Collectively, these advances underscore Vietnam’s growing leadership in regenerative medicine and the integration of CGT into mainstream healthcare.

Preclinical and clinical trials of CGT in Viet Nam

Over the past decade, CGT in Vietnam has made remarkable progress, transitioning from pioneering research to clinical implementation and national strategic planning. Currently, Viet Nam has developed a nationwide network of hospitals performing hematopoietic stem cell transplantation and MSC–based therapies, with dozens of clinical trials conducted across multiple disease indications [8-12].

Based on published data, Vietnamese centers have collectively performed at least several hundred HSCT procedures, including over 500 cases nationwide by 2017–2018 and 547 procedures at the National Institute of Hematology and Blood Transfusion alone by 2022 [9, 13]. In this context, Vietnam has also reported its first successful HSCT for children with WAS [1].

MSC-based therapy, especially using adipose-derived mesenchymal stem cells (AD-MSCs), has become a cornerstone of translational research and clinical application in Vietnam. In Vietnam, the application of autologous AD-MSCs is gaining traction, with early clinical observations indicating acceptable safety profiles and practical feasibility, particularly in conditions linked to age-related inflammation. Complementing these findings, experimental studies suggest beneficial effects in cartilage regeneration and immune-driven dermatologic disorders. Notably, a phase I, open-label, single-arm clinical investigation carried out in Ho Chi Minh City explored the biological impact and safety of infusing autologous AD-MSCs in individuals experiencing chronic low-grade inflammation and metabolic complications associated with aging. In this study (NCT05827757), twelve patients received two intravenous infusions of 100 million autologous AD-MSCs each, with the trial strictly adhering to Vietnamese Good Clinical Practice guidelines and Ministry of Health approval [2]. No adverse events were reported throughout the follow-up period, indicating a favorable safety profile.

By day 180, a pronounced shift in the biological profile was observed: levels of key pro-inflammatory mediators—including tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, IL-1α, and IL-8—were substantially reduced, while ratios reflecting anti-inflammatory activity (such as IL-4/IL-10 and IL-2/IL-10) showed a corresponding increase [2]. Taken together, these immunologic shifts indicate that systemic infusion of AD‑MSCs represents a safe strategy with meaningful immunomodulatory potential for controlling age‑related inflammation [2, 14].

Vietnamese pediatric centers have recently initiated curative HSCT programs for children with rare immunodeficiencies such as WAS. A retrospective series at Vietnam National Children’s Hospital reported 15 allogeneic HSCT procedures in 13 children with WAS between 2020 and 2024. A minority of procedures employed reduced-intensity conditioning (26.7%), whereas the majority were preceded by myeloablative regimens (73.3%) [1]. The origin of donors varied considerably, comprising mismatched related individuals (40%), unrelated cord blood units (33.3%), matched sibling donors (20%), and a smaller fraction from phenotypically identical family members (6.7%) [1]. Median times to engraftment were 14 days for neutrophils and 48 days for platelets. By day +100, about 77% of patients had established full donor chimerism, and overall survival reached 92.3% [1]. The main cause of mortality was chronic graft-versus-host disease (GVHD). Additionally, a separate published case documented a successful haploidentical HSCT with post-transplant cyclophosphamide for WAS, resulting in full immune reconstitution and no GVHD at 32 months follow-up [15]. These outcomes demonstrate that complex allogeneic HSCT, including haploidentical transplantation, is now a feasible and effective treatment option for non-malignant diseases in Vietnam [1, 9, 15].

Whether persistent neurological deficits after ischemic stroke could be mitigated was examined in a phase II randomized controlled trial, which evaluated the effects of delivering allogeneic umbilical cord–derived mesenchymal stem cells (UC-MSCs) either through intrathecal administration into the cerebrospinal fluid or via systemic intravenous infusion. Thirty‑two individuals aged 40–75 years with established post‑stroke sequelae were allocated to receive UC‑MSCs: 16 were treated with two intrathecal administrations plus a standardized rehabilitation program, and 16 with two intravenous infusions plus the same rehabilitation regimen, while a further 16 matched participants underwent rehabilitation alone without UC‑MSC therapy [16]. UC‑MSC treatment was administered at a dose of 1.5 × 10⁶ cells/kg at two time points (study entry and month 3).

Follow‑up continued for 12 months, during which neurological and functional outcomes were serially assessed using standard stroke severity (NIHSS), functional independence (FIM), spasticity (MAS), motor function (FMS), and quality-of-life (SF-36) scales [16]. No serious treatment-related complications were detected, and participants receiving cells intravenously experienced fewer adverse events than those treated intrathecally [16]. By the 6‑month visit, the intravenous cohort had already achieved statistically meaningful improvements on the SF‑36, FIM, and NIHSS scales, and by 12 months, both stem-cell-treated groups had significant clinical and quality-of-life improvements compared with baseline, with larger benefits in the intravenous arm, particularly for SF-36 [16]. When compared with rehabilitation alone, enhancements in neurological function and quality of life were observed alongside a favorable safety profile for both delivery routes of UC-MSCs. Among these approaches, systemic intravenous administration demonstrated the most advantageous combination of therapeutic effect and tolerability [16].

Parallel to clinical advances, preclinical and mechanistic studies are addressing key challenges in efficacy and safety. Interestingly, an in vitro work systematically dissects how MSCs trigger coagulation, supporting its role as a mechanistic investigation of thrombosis risk [17]. Quantitative profiling of tissue factor (TF) and a panel of pro‑ and anticoagulant regulators was performed in mesenchymal stromal cells maintained under xeno‑ and serum‑free conditions and derived from dental pulp, adipose tissue, umbilical cord, and bone marrow, revealing pronounced dependence of TF, collagen type 1 alpha 1 chain (COL1A1), phosphatidylserine, tissue factor pathway inhibitor (TFPI), and prostaglandin I2 receptor (PTGIR) expression [17]. Using plasma-based clotting assays, Hoang and colleagues found that MSCs from multiple tissue sources could directly trigger fibrin clot generation in normal donor plasma; this procoagulant effect was only partly attenuated by blockade with an anti–tissue factor monoclonal antibody, and, importantly, even human umbilical vein endothelial cells lacking detectable TF expression were still capable of displaying measurable coagulation activity in vitro [17]. Together, these experiments clarify the cellular and molecular mechanisms underlying MSC-associated coagulation, and explain why TF expression alone is an incomplete predictor of thrombotic risk.

Other disease models such as psoriasis-like inflammation [3] provide insights into dose-response relationships and immunomodulatory mechanisms, helping to refine therapeutic protocols before large-scale clinical trials.

Another key achievement is the diversification of therapeutic strategies beyond conventional cell transplantation. Vietnam has increasingly explored cell-free approaches, particularly exosome-based therapies. Derived from AD-MSCs, exosomal preparations have been applied as a cell‑free therapy that not only hasten closure and regeneration of cutaneous wounds but also counteract UV‑induced skin aging changes in both animal models and early-stage trials [5, 6]. These findings support the growing interest in cell-free approaches, especially exosome-based therapies, which offer regenerative and anti-aging effects while potentially presenting fewer safety concerns compared to whole-cell transplantation. Building on this direction, research teams in Viet Nam have generated extracellular vesicles from human fibroblasts engineered to express ETV2. These vesicles drive robust endothelial proliferation in vitro and markedly augment neovessel formation in a mouse hindlimb ischemia model, pointing to a powerful cell‑free modality for therapeutic vascular regeneration [18]. In addition, efforts to optimize stem cell sources and quality represent another important area of progress. Techniques such as hypoxia-induced enhancement and selective enrichment of specialized subpopulations (e.g., Muse cells) have been explored [7]. Moreover, hypoxic culture combined with ETV2 overexpression markedly increases the efficiency of directly reprogramming fibroblasts into functional endothelial progenitor cells, offering an improved source for ischemic therapies [19]. Alongside advances in characterization methodologies [20], these studies contribute to improving reproducibility, potency, and standardization, critical factors for regulatory approval and clinical scalability. Collectively, these achievements reflect Vietnam’s ability to keep pace with global trends, positioning the country at the forefront of cutting-edge developments in CGT.

Additionally, combinatorial strategies integrating supportive biologics have also been investigated. Within regenerative orthopedics, evidence points to a cooperative therapeutic effect when adipose-derived stem cell transplantation is paired with activated platelet-rich plasma. This combination appears to enhance stem cell engraftment and cartilage repair, suggesting a synergistic approach to regenerative therapy [4]. Although such strategies remain relatively limited in recent Vietnamese publications, they highlight an emerging interest in improving therapeutic outcomes through multi-component systems. Several constraints persist notwithstanding these advances: the majority of clinical investigations remain limited to early-stage or small cohorts, and robust confirmation of efficacy is hindered by the scarcity of large-scale randomized controlled trials.

Standardization of protocols, long-term safety monitoring, and harmonization with international regulatory frameworks are ongoing challenges.

Within the country, the development of cutting-edge interventions, such as gene-engineered cellular treatments exemplified by CAR-T, remains at an early, formative stage, indicating that these approaches have yet to achieve widespread clinical maturity.

Summary

In summary, Vietnam has made substantial progress in recent years by establishing clinical feasibility, advancing mechanistic insights, and adopting next-generation therapeutic approaches in cell and stem cell therapy. While the field is still developing, the current trajectory suggests strong potential for Vietnam to become a significant regional contributor to regenerative medicine, provided that future efforts focus on scaling clinical evidence, standardization, and regulatory maturity. One of the most notable achievements is the expansion of clinical applications, particularly MSCs and hematopoietic stem cells. Early-phase clinical work [2], demonstrates that locally developed therapies can meet initial safety and feasibility benchmarks in human subjects. In parallel, the successful implementation of HSCT for rare diseases [1], reflects increasing clinical sophistication and the ability to manage complex, high-risk procedures within the national healthcare system. These milestones indicate that Vietnam is no longer limited to preclinical investigation but is actively delivering advanced therapies in clinical settings.

References

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