The demand for the CGT workforce exceeds the capacity of current training programs to produce professionals ready for Good Manufacturing Practice (GMP) operations and associated quality and regulatory requirements. Most academic programs build strong scientific foundations but do not consistently prepare learners for process development and disciplined practice within regulated quality systems, resulting in prolonged onboarding and variable early performance. This gap reflects not only the specialized operational demands of CGT, but also the fact that most universities are designed to provide broad scientific education rather than role-specific preparation for a single employment sector. We synthesized a literature- and stakeholder-informed CGT Education Framework comprising five mutually reinforcing pillars: (i) curriculum innovation that embeds quality and GMP principles, (ii) interdisciplinary integration across science, engineering, and regulation, (iii) inclusive and scalable delivery approaches, (iv) structured experiential learning in GMP-aligned settings, and (v) competency-based credentialing. An accompanying implementation roadmap defines role-specific actions, timelines, and measurable workforce readiness outcomes, while case studies and short-format training exemplars illustrate practical application. Together, these recommendations provide a pathway to align academic preparation with the technical, regulatory, and quality-compliance demands of CGT, improve time-to-productivity, and support global workforce mobility. They move the field from ad hoc initiatives to a coherent, outcomes-driven approach that builds a pipeline of resilient, industry-ready talent.

Umbilical cord blood (UCB) is a rich source of hematopoietic stem and progenitor cells (HSPCs), mesenchymal stromal cells (MSCs), and diverse immune cell subsets with unique developmental and functional properties. These characteristics have established UCB as an important graft source for hematopoietic stem cell transplantation (HSCT) and an emerging platform for next-generation immunotherapies and regenerative applications. Importantly, cord blood transplantation remains most widely used in pediatric patients, who constitute the majority of UCB transplant recipients due to favorable tissue compatibility and hematopoietic reconstitution kinetics and the suitability of single-unit UCB grafts. Advances in donor recruitment, processing, cryopreservation, ex vivo expansion, and cell engineering continue to broaden the clinical utility of UCB while addressing historical limitations related to cell dose and engraftment kinetics. This review summarizes current biological insights, key aspects of banking infrastructure and the regulatory landscape, established and investigational therapeutic uses, and the evolving challenges and opportunities that will shape the future integration of UCB usage beyond graft source for HSCT.

As a second-line treatment for first-line steroid-refractory acute GVHD, ruxolitinib was proven to be significantly more effective than control therapies (nine commonly used therapy options) in a prospective, randomized trial. However, it could sometimes be difficult to administer ruxolitinib for patients with cytopenia or who have difficulty taking it orally regularly. The present retrospective study compared the outcomes of second-line mesenchymal stromal cell (MSC) and antithymocyte globulin (ATG) therapies following first-line steroid therapy for acute GVHD. Clinical data for the total 1120 patients who received MSC (n = 777) and ATG (n = 343) as second-line therapy following first-line steroid therapy for acute GVHD from 2016 to 2022, when both therapies were covered by health insurance in Japan, were extracted from Japanese stem cell transplantation registry data. Overall response rates (ORRs) on day 28 of the MSC and ATG therapies were 62.7% and 51.0%, respectively (multivariate analysis: odds ratio, 1.56; P = 0.001). ORRs for skin, liver, and gastrointestinal tract acute GVHD were 66.3% versus 57.5% (1.43, P = 0.063), 33.1% versus 25.7% (1.18, P = 0.636), and 66.3% versus 49.8% (1.96, P < 0.001), respectively. The incidences of invasive fungal infection and viral infection within the first 100 days after the start of second-line therapy were 3.9% versus 8.2% (Fisher's exact test: P = 0.005) and 13.4% versus 25.1% (P < 0.001), respectively. However, non-relapse mortality, the relapse rate, and overall survival did not differ between MSC and ATG therapies. Furthermore, the propensity score-matched analysis yielded results consistent with the findings described above. In conclusion, this retrospective study demonstrated that the ORR based on whole body assessment and the ORR based on gastrointestinal tract stage assessment were both significantly higher with MSC therapy than with ATG therapy. However, prospective, randomized, controlled trials are necessary for a more accurate comparison.

CRISPR/Cas9-mediated nonviral targeted integration via homology-directed repair (HDR) offers a strategy for generating uniform, next-generation chimeric antigen receptor (CAR) T cells while avoiding risks associated with viral vectors. However, efficient delivery of large therapeutic payloads into primary T cells is limited by low HDR efficiency and electroporation-induced toxicity. Here, we show that sequential CD2/CD3/CD28 activation improves HDR-mediated large-payload knock-in at the T cell receptor α constant (TRAC) locus and increases viable CAR-T cell yield under an AZD7648-supported nonviral editing framework. Transcriptomic profiling and mitochondrial membrane potential analysis suggest that this condition is associated with cell-cycle- and metabolism-related programs, which may contribute to improved tolerance to electroporation stress and processing of large DNA templates. Functionally, engineered nonviral TRAC-CD19.CAR-T cells exhibit antigen-specific cytotoxicity in vitro and suppress leukemia progression in an NSG xenograft model, with antitumor activity that approached that of a lentiviral CAR-T reference in this proof-of-function xenograft model. This work establishes an optimized sequential activation strategy to improve nonviral, large-payload TRAC-targeted CAR-T cell engineering and may inform future development of precision cellular immunotherapy manufacturing workflows.

Post-transplant cyclophosphamide-based haploidentical transplantation (PTCy-haplo) and umbilical cord blood transplantation (uCBT) have the potential to mitigate the adverse impact of pretransplant measurable residual disease (MRD) on post-transplant survival of patients with acute myeloid leukemia (AML). To compare outcomes between PTCy-haplo and uCBT in patients with MRD-positive AML, we retrospectively analyzed MRD-positive AML patients aged ≥16 years enrolled in the Japanese nationwide registry from 2015 to 2023 who underwent PTCy-haplo (n = 94) or single uCBT (n = 275) as first transplantation. MRD was evaluated by polymerase chain reaction for chimeric genes (n = 139) or Wilms' tumor 1 expression (n = 230). In multivariable analyses, the PTCy-haplo and uCBT groups showed comparable relapse-free survival (RFS) (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.67‒1.67; P = 0.809), overall survival (HR, 0.92; 95% CI, 0.57‒1.49; P = 0.735), graft-versus-host disease (GVHD)-free RFS (HR, 0.89; 95% CI, 0.61‒1.31; P = 0.560), chronic GVHD (cGVHD)-free RFS (HR, 1.20; 95% CI, 0.81‒1.78; P = 0.368), relapse (HR, 0.78; 95% CI, 0.39-1.57; P = 0.490) and nonrelapse mortality (HR, 1.48; 95% CI, 0.79-2.79; P = 0.230). Compared to the uCBT group, the PTCy-haplo group showed lower incidences of grade II‒IV (HR, 0.60; 95% CI, 0.39-0.92; P = 0.020) and III‒IV acute GVHD (aGVHD) (HR, 0.28; 95% CI, 0.10-0.79; P = 0.016), but a higher incidence of extensive cGVHD (HR, 2.23; 95% CI, 1.16-4.29; P = 0.017). Furthermore, higher likelihoods of neutrophil (HR, 2.12; 95% CI, 1.61-2.80; P < 0.001) and platelet engraftment (HR, 1.96; 95% CI, 1.39-2.76; P < 0.001) were observed in the PTCy-haplo group. In subgroup analysis, uCBT was associated with improved RFS in AML with poor cytogenetic risk (HR for PTCy-haplo versus uCBT, 2.49; 95% CI, 1.04-5.97; P for interaction = 0.032). In conclusion, survival outcomes were comparable between PTCy-haplo and uCBT in patients with MRD-positive AML. PTCy-haplo was associated with a lower risk of aGVHD, a higher risk of cGVHD and superior hematopoietic engraftment. In the subgroup of patients with poor cytogenetic risk, uCBT was associated with improved RFS.

Chronic lung diseases remain a leading cause of morbidity and mortality worldwide, yet few therapies restore damaged lung tissue or halt disease progression. Cell-based therapies offer a potential strategy to address this gap by replacing or repairing disease-causing cell populations within the lung. Advances in stem cell biology, gene editing and regenerative medicine across multiple organ systems have established key principles for successful cellular therapies, including the identification of tissue stem/progenitor populations, the control of progenitor cell differentiation ex vivo and the enabling of homing and engraftment of exogenous cells within host tissues. In the lung, growing insight into epithelial regeneration, particularly the roles of airway basal cells and alveolar type 2 cells as resident progenitors, has provided a biological rationale for cell replacement approaches. Recent preclinical studies demonstrate that transplanted epithelial progenitors can engraft, differentiate and contribute to functional airway or alveolar repair in animal models. Progress in macrophage transplantation for pulmonary alveolar proteinosis illustrates how disease-specific cellular therapies may translate toward clinical application. However, significant challenges remain, including efficient cell delivery to the lung, enhancing cell retention and performing safe niche preconditioning to permit engraftment. In this review, we summarize the biological foundations of lung regeneration, recent advances in lung cell-based therapies and emerging strategies for delivery, engraftment and translation to the clinic. Together, these developments suggest that regenerative cell therapies may ultimately provide disease-modifying treatments for both genetic and acquired lung diseases.

Induced pluripotent stem cells (iPSCs), which can be applied to disease modeling, regenerative medicine, and cultivated meat, among other uses, have opened a new era in the biomedical field. To obtain sufficient high-quality cells for these applications, a current good manufacturing practice (cGMP)-compliant large-scale expansion is necessary. It indicates that the entire process for producing iPSCs should adhere to cGMP regulations, encompassing both upstream steps, such as raw material collection, reprogramming, and large-scale expansion, as well as downstream steps, including harvesting, concentrating, and cryopreserving the cells. Importantly, well-established critical quality attributes are mandatory to ensure the quality of the produced cells. For decades, huge efforts have been made to initiate and develop each step of the process. However, there are still limitations and obstacles that slow down the progress of the cGMP large-scale production of iPSC. Therefore, in this review, we summarize the accomplishments and challenges of current technologies involved in making applicable and clinical iPSCs. Throughout this, future directions and solutions can be suggested for the production of large-scale, high-quality iPSCs.