Cell Therapy in Regenerative Medicine, 2026 and Beyond
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Updated on 5/18/2026
Articles from a Special Edition of Cells on Regenerative Cell Therapy
Recently a special Edition in the MDPI Journal Cells was published curating eleven open access articles of note on “Gene and Cell Therapy in Regenerative Medicine”, highlighting key directions the field is heading toward. A summary of the editorial on this Special Issue is given below:
From: Rizvanov AA, Doğan A. Gene and Cell Therapy in Regenerative Medicine. Cells. 2026 Jan 23;15(3):212. doi: 10.3390/cells15030212. PMID: 41677579; PMCID: PMC12896639
Gene and cell therapies have become core components of regenerative medicine, moving from proof-of-concept studies toward clinically actionable strategies for repairing or replacing damaged tissues. In parallel with the expansion of approved advanced therapy medicinal products, the field is also redefining what “regeneration” means in practice—ranging from enhanced endogenous repair and functional recovery to cell replacement and, increasingly, engineered biological substitutes.
This Special Issue, “Gene and Cell Therapy in Regenerative Medicine” (https://www.mdpi.com/journal/cells/special_issues/GeneCellTherapy_Regenerative accessed on 16 January 2026), brings together 11 open-access publications (7 original research articles and 4 reviews) that reflect key directions in the field: (i) improvement in gene- and cell-product manufacturing workflows; (ii) understanding how tissue microenvironments shape therapeutic performance; (iii) integration of biomaterials with living therapeutics; and (iv) progress in delivery technologies and cell sources relevant to translational regenerative medicine.
2. Field Advances and Trends in 2024–2025
The 2024–2025 period has been marked by several developments that are directly relevant to regenerative medicine, particularly at the interface of gene delivery, cell replacement, immune engineering, and scalable manufacturing.
Expansion of Pluripotent Stem Cell-Derived Therapeutics and Movement Toward Later-Stage Development
A central trend has been the continued growth of human pluripotent stem cell (hPSC)-derived products in interventional trials. A 2025 landscape analysis reported 115 regulatory-approved clinical trials testing 83 hPSC products (as of December 2024), with >1200 patients dosed and no “generalizable” safety concerns identified to date—while emphasizing that long-term follow-up and product-specific risks remain essential considerations [1].
Type 1 diabetes (T1D) has emerged as a particularly informative indication for regenerative medicine because it requires durable engraftment, physiological responsiveness, and acceptable risk–benefit profiles. In 2024, device-based delivery of stem cell-derived β-cell precursors demonstrated that, in a subset of recipients, measurable C-peptide production could correlate with improved glucose-control metrics, while also highlighting the persistent challenges of cell survival, vascularization, and effective functional mass in humans [2].
In 2025, a multicenter study of an allogeneic stem cell-derived, fully differentiated islet-cell therapy (zimislecel) reported engraftment and functional C-peptide detection across treated participants, with clinically meaningful outcomes in the analyzed cohort, including insulin independence in a majority at one year (interim analyses), while also underscoring immunosuppression-related risks [3].
Immune Engineering as an Enabling Layer for “Off-the-Shelf” Regeneration
A major barrier for allogeneic cell replacement remains immune rejection. A key research direction in 2024–2025 has been immune engineering (hypoimmune or immune-evasive designs) intended to reduce or eliminate the need for chronic immunosuppression. In a 2024 primate-focused study, hypoimmune iPSC-derived products showed prolonged survival in immunocompetent, allogeneic settings, supporting the concept that immune engineering can function as a platform technology for scalable cell replacement [4].
Delivery Innovation and the Rise of In Vivo Editing as a Regenerative Tool
The regenerative impact of gene therapy is increasingly constrained (or enabled) by delivery. Beyond classic viral-vector paradigms, 2024 saw progress in lipid nanoparticle (LNP) reformulation strategies intended to achieve organ-targeted mRNA accumulation and translation while mitigating off-target distribution, which remains a critical translational bottleneck for systemic nucleic-acid therapeutics [5].
Concurrently, clinical data continue to strengthen the feasibility of in vivo genome editing with clinically relevant endpoints. In late 2024, a first-in-human study in ATTR cardiomyopathy reported rapid and durable reductions in circulating transthyretin following a single administration of a CRISPR-Cas9 therapy, illustrating the maturation of in vivo editing platforms that may ultimately be adapted to regenerative indications where durable pathway modulation is needed [6].
Regulatory Milestones Relevant to Tissue Repair Indications
Regulatory activity can reshape translational priorities. In June 2024, the FDA expanded approval of an AAV-based gene therapy for Duchenne muscular dystrophy (Elevidys) to include a broader population (ambulatory and non-ambulatory individuals aged ≥ 4 years), reflecting both the clinical demand for systemic gene delivery and the continuing evolution of evidence frameworks for high-need indications [7].
Xenotransplantation Enabled by Multiplex Gene Editing: Toward Organ Replacement Pathways
A distinct but closely related track of regenerative medicine is the development of gene-edited donor organs as a pragmatic response to organ shortages. In 2024, the first transplantation of a gene-edited pig kidney into a living human recipient was reported as a notable milestone for the field [8]. In 2025, FDA clearance for initial multi-patient clinical trials of genetically modified pig kidneys was reported, signaling movement from individual compassionate-use experiences toward structured clinical evaluation [9].
Overview of Contributions in This Special Issue
The published papers in this Special Issue can be grouped into three overlapping themes: (i) enabling technologies for gene and cell therapy manufacturing and deployment; (ii) cell therapy and microenvironmental determinants of regeneration; and (iii) reviews addressing delivery platforms and cell sources for translational regenerative medicine.
3.1. Enabling Strategies for Gene Therapy and Gene Delivery in Regenerative Contexts
Ex vivo expansion as a manufacturing lever for gene therapy: Fleischauer et al. investigated the use of the TGF-β inhibitor A83-01 to enhance murine hematopoietic stem and progenitor cell (HSPC) expansion, a relevant enabling step for gene therapy workflows where cell yield and functional preservation influence feasibility and cost. Such approaches are particularly important as the field seeks to standardize potency, improve transduction/editing consistency, and reduce variability in cell starting material [10].
BMP2 gene delivery for bone regeneration: Bukharova et al. compared adenovirus-based BMP2 gene delivery delivered in vivo versus ex vivo for bone regeneration. By explicitly contrasting these two routes, the study addresses a practical translational question: whether local in situ gene transfer or cell-mediated ex vivo delivery offers superior control over efficacy and safety in tissue repair settings [11].
Context-dependent responses in therapeutic angiogenesis/repair: Stafeev et al. evaluated combined HGF/VEGF gene therapy for limb ischemia in mice with impaired glucose tolerance, reporting a shift in regenerative response patterns. This work highlights how metabolic comorbidity can modify the balance between angiogenic, neurotrophic, and metabolic remodeling outcomes—an issue that remains central to real-world regenerative medicine, where patient heterogeneity frequently drives variable responses [12].
3.2. Cell Therapies, Tissue Microenvironments, and Biomaterial Support
Regeneration in sensory tissue via local cell administration: Ishikura et al. examined nasal administration of murine adipose-derived stem cells in a mouse model of olfactory epithelium damage. The study contributes to the broader theme that route of administration and local tissue context can be decisive for cell-therapy efficacy in neural and sensory regeneration [13].
Microenvironmental determinants in osteoarthritis-relevant cell therapy: Kitajima et al. showed that synovial fluid from human knee osteoarthritis can increase the viability of human adipose-derived stem cells, with mechanistic association to FOSL1 upregulation. These findings align with the growing view that “cell therapy performance” is not solely a property of the cell product but also of the disease microenvironment, supporting the rationale for patient stratification, preconditioning strategies, and microenvironment-aware potency assays [14].
Large-animal stromal cell biology and heterotopic tissue formation: Petinati et al. reported that porcine bone marrow multipotent mesenchymal stromal cells, implanted under the kidney capsule, can form an ectopic focus containing bone, hematopoietic stromal microenvironment, and muscle tissue. Such observations are relevant for translational model development, for understanding stromal cell plasticity in vivo, and for anticipating ectopic differentiation risks during regenerative applications [15].
Biomaterial–cell combinations for challenging wound-healing settings: Nie et al. investigated supramolecular hydrogel-wrapped gingival mesenchymal stem cells in cutaneous radiation injury. The work fits a broader trend toward “cell therapy plus matrix” designs, where biomaterials can improve local retention, viability, and paracrine persistence, while also enabling more controllable delivery in compromised tissues [16].
3.3. Reviews: Cell Sources, Omics-Informed Differentiation, and Gene Delivery Platforms
Red blood cells from hPSCs: Lee et al. reviewed progress in generating red blood cells from human pluripotent stem cells, emphasizing persistent challenges that are also relevant to other cell replacement products (maturation, scalability, and quality controls) [17].
Transcriptomics for differentiation control and quality assurance: Ogi and Jin discussed transcriptome-powered differentiation, reflecting the increasing role of single-cell and bulk transcriptomic frameworks for defining cell identity, detecting off-target states, and building quality-by-design pipelines for regenerative products [18].
AAV serotypes and gene therapy applications: Issa et al. summarized AAV serotypes and their use in gene therapy, a foundational topic for regenerative medicine where long-term expression and tissue tropism remain central design constraints [19].
Cell sources for retinal regeneration and translation challenges: Grigoryan reviewed cell sources for retinal regeneration and discussed translation-relevant considerations. Retinal indications remain one of the most active areas for regenerative development because they offer relatively accessible target tissues and quantifiable functional endpoints, while still posing major challenges in integration, durability, and immune compatibility [20].
4. Conclusions and Outlook
Across its research articles and reviews, this Special Issue underscores several recurring messages. First, regenerative outcomes depend on more than the selected vector or cell type: manufacturing constraints, delivery route, and tissue microenvironment can be equally decisive. Second, the field is moving toward platform thinking, where immune engineering, omics-driven quality control, and rational delivery design serve as reusable layers across multiple indications. Third, the most visible breakthroughs of 2024–2025—late-stage pluripotent stem cell therapeutics, improved delivery methods for nucleic acids, in vivo editing clinical data, and gene-edited organ replacement initiatives—collectively point to a near-term future in which regenerative medicine will increasingly be implemented as an engineered, combination technology rather than as a single modality.
Updated on 5/17/2026
An Update on US Regulatory Issues and Guidance on Use of Cell Therapy in Regenerative Medicine
Source: https://www.nist.gov/regenerative-medicine-and-advanced-therapy
What is regeneratvie medicine and advanced therapy?
Regenerative medicine therapy, including cell therapy, gene therapy, and therapeutic tissue engineering, provides unprecedented potential to treat, modify, reverse, or cure previously intractable diseases, such as cancer and organ failures. This class of therapy has completely changed the paradigm and the trajectory for medical treatment. Broad clinical translation and patient access requires advances in manufacturing technologies and measurements to ensure the safety, quality, and consistency of the therapy and to reduce the cost.
What is NIST doing?
The National Institute of Standards and Technology (NIST) is committed to solving the measurement challenges of this fast-moving sector of the bioeconomy by providing underpinning measurement infrastructure and platform technologies, as well as standards to promote manufacturing innovation, improve supply chain resilience, and support characterization and testing to facilitate regulatory approval.
The NIST Regenerative Medicine program is working closely with the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research (FDA/CBER) and the Standards Coordinating Body (SCB) as well as the broader industry to develop global manufacturing and measurement standards underpinned by a robust measurement infrastructure needed to advance product development and translation as directed by Sec. 3036 of the 21st Century Cures Act.
The NIST laboratory programs support this growing industry as well as the broader industry ecosystem by:
- Developing new methods for quantitative measurement of quality attributes of a broad range of starting materials, products, and critically needed reagents for applications such as cellular immunotherapies as living drugs, viral and non-viral vectors and delivery vehicles, and advanced genome editing tools and genome edited biological systems.
- Providing reference materials, including complex living reference materials, and documentary standards through international and national standards development organizations as well as professional societies.
- Applying measurement assurance strategies and associated tools to improve the performance of complex biological measurements systems.
- Convening stakeholders on precompetitive measurement and manufacturing challenges.
- Establishing partnership across the public and private sectors to develop measurement solutions, platform technologies, and standards.
Selected Programs and Accomplishments
NIST has developed a suite of standards and tools for characterizing biological systems and components using advanced measurement science strategies that enable the generation of high-quality data. Some recent examples of NIST’s work include:
- Design of Fit-For-Purpose Assays: As regenerative medicine therapy represents a broad and diverse range of products using living cells as the starting material and/or the product, NIST led the development of an ISO standard that provides considerations for characterization of cellular therapeutic products, including approaches to select and design analytical methods that are fit-for-purpose. These considerations are intended to guide the establishment of critical quality attributes for a cellular therapeutic product. NIST is developing similar concepts for the measurement of nucleic acids, viral vectors, and other biological systems and entities.
- Cell Counting Measurements: Count is the most foundational metric for assessing the attributes of cells, yet one of the least harmonized measurements. NIST developed innovative measurement solutions for evaluating the quality of cell counting measurements through experimental design and statistical analysis that led to two ISO international standards as well as tools to facilitate their adoption. The standards are used by industry for cell count and characterization to support CTP testing for safety and efficacy.
- o ISO 20391-1:2018 Cell counting Part 1: General guidance on cell counting methods
- o ISO 20391-2:2019 Cell counting Part 2: Experimental design and statistical analysis
- o Cell Counting Method Evaluation Tool (COMET): NIST developed an online Counting Method Evaluation tool for executing the statistical analysis and reporting outlined in ISO 20391-2:2019.
- NIST Flow Cytometry Standards Consortium: Flow cytometry is used to analyze individual cells to understand the proteins, nucleic acids, and other biomolecules they have or produce, and to analyze groups of cells to differentiate among different cell types and lineages. Flow cytometry is the most common analytical tool used in the characterization and testing of curative cellular immunotherapy products. Established in 2020, the NIST Flow Cytometry Consortium is working with leaders in cell therapy development and manufacturing, U.S. government, global regulators, scientific societies, and the broader biotech industry to develop measurements, standards, and technology needed to accelerate the translation, manufacturing, and approval of new therapies (e.g., CAR-T and emerging stem cell derived allogenic therapy). The Consortium coordinates strategic inter-laboratory testing and comparisons to develop critical standardized flow cytometry assays for the regenerative medicine and biotechnology industry.
- NIST Rapid Microbial Testing Methods (RMTM) Consortium: Established in 2020, this Consortium is working with experts across the regenerative medicine field to address the need for measurements and standards, including reference materials, to increase confidence in the use of rapid testing for microbial contaminants in regenerative medicine and advanced therapy products.
- NIST Genome Editing Consortium: Established in 2018, this Consortium supports the development of groundbreaking tools and standards required to detect and monitor the accuracy and precision of genome editing technologies for the U.S. and global biotechnology sectors. The Consortium has developed a standard genome editing lexicon, with 42 defined terms, that is being referenced by industry in active regulatory filings.
- ISO 5058-1:2021 Biotechnology: Genome Editing – Part 1: Vocabulary
- VCN Interlaboratory Testing Program: The copy number of integrated genomic DNA is critical for assessing the safety and efficacy of engineered cellular therapeutic products such as CAR-T. NIST is leading an interlaboratory testing program to evaluate the suitability and utility of cell lines with discrete number of integrated lentiviral vector copy number (VCN) and associated DNA materials to serve as reference materials or controls for a variety of cellular and genomic measurements.
- Quantitative and Advanced Bioimaging: NIST developed a comprehensive bioimaging program to support the use of imaging to better understand the fundamental mechanism-of-action of therapeutic cells and visualize dynamic and heterogeneous biological processes and interactions. Examples include the application of quantitative imaging and AI to assess the quality of tissue engineered medical products in a GMP setting as well as reference materials for instrument qualification and, data sets to benchmark AI/ML algorithm development. NIST developed tools and guidelines for performing quantitative fluorescence imaging, supporting a critical measurement platform for the characterization of biological processes.
- ASTM F3294 – 18 Standard Guide for Performing Quantitative Fluorescence Intensity Measurements
- Next Generation Metrics for Cell-Based Therapies and Regenerative Medicines
- Prototype Cell Assay Measurement Platform (P-CAMP): The NIST P-CAMP is a unique automated platform that enables multimodal analysis of large parameter spaces and guides the development of measurement assurance strategies for assays used for characterization and testing of biological products and processes.
- Assay for Monitoring Patient Response to Therapy: NIST is collaborating with NIH/NCI to develop quantitative and comparable flow cytometric procedures for establishing clinical cut-off points needed to monitor patient response to a broad range of therapies including cellular immunotherapies.
Updated on 2/24/2026
Sickle Cell Gene Therapies Casgevy and Lyfgenia Still Lacking Traction 2 Years In – BioSpace
2012pharmaceutical
sjwilliamspa
The struggles of gene therapies continue. Here is a very nice article where Biospace interviews Courtney Rice regarding the commercial status of marketed gene therapies.
Heather MacKenzie of BioSpace writes:
” Last year, just 64 patients with sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT)—for which Casgevy was greenlit in January 2024—received infusions of the gene therapy, according to Vertex’s full-year 2025 earnings report. An additional 147 people had their first cell collection. Meanwhile, Genetix Bio—formerly bluebird bio—has treated over 100 patients with Lyfgenia, which is only approved for SCD, a member of Genetix’s executive team told BioSpace in an email.”
Foreseeing low adoption rates was somehow overlooked when modeling the economics early on as gene therapies were heralded as scientific breakthroughs.
What wasn’t taken into consideration was the patient journey required for conditioning prior to treatment, a process that is lengthy, painful and could lead to infertility.
“You’re asking a lot of time for these patients to be out of the game, both from the conditioning time to the procedure to the engraftment,” Rice said of the new gene therapies. “And that somehow sort of got glossed over in the parade, in the champagne shaking and excitement.”
I recall Stuart Orkin once say – there is a difference between treating a disease and relieving a disease burden. The two shouldn’t get mixed up.
Will adoption increase in the future? Time will tell, but many pharmas loath carrying low-profit drugs that generate inefficient returns on the bottom line.
The full article is worth reading here –
https://lnkd.in/eTC58tMN