Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on behalf of The American Society of Transplantation and Cellular Therapy and the European Society of Blood and Marrow Transplantation.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project. Key statements/recommendations are as follows: 1) Autologous HCT is recommended as an option for consolidation therapy in patients with progression of untransformed disease within 24 months of front line chemoimmunotherapy and upon achieving a complete (CR) or partial response (PR) to salvage second line therapies; 2) CAR-T is considered as a treatment option for patients who did not achieve CR or PR after second or subsequent lines of therapies; 3) Allogeneic HCT is considered as consolidative treatment in relapsed FL patients with chemosensitive disease who have received 3 or more lines of systemic therapy and are the following clinical scenarios: post CAR-T failure; lack of access to CAR-T or have therapy related myeloid neoplasm. These clinical practice recommendations will help guide clinicians managing patients with FL.

Modifying the Secretome of Mesenchymal Stem Cells Prolongs the Regenerative Treatment Window for Encephalopathy of Prematurity.

Clinical treatment options to combat Encephalopathy of Prematurity (EoP) are still lacking. We, and others, have proposed (intranasal) mesenchymal stem cells (MSCs) as a potent therapeutic strategy to boost white matter repair in the injured preterm brain. Using a double-hit mouse model of diffuse white matter injury, we previously showed that the efficacy of MSC treatment was time dependent, with a significant decrease in functional and histological improvements after the postponement of cell administration. In this follow-up study, we aimed to investigate the mechanisms underlying this loss of therapeutic efficacy. Additionally, we optimized the regenerative potential of MSCs by means of genetic engineering with the transient hypersecretion of beneficial factors, in order to prolong the treatment window. Though the cerebral expression of known chemoattractants was stable over time, the migration of MSCs to the injured brain was partially impaired. Moreover, using a primary oligodendrocyte (OL) culture, we showed that the rescue of injured OLs was reduced after delayed MSC coculture. Cocultures of modified MSCs, hypersecreting IGF1, LIF, IL11, or IL10, with primary microglia and OLs, revealed a superior treatment efficacy over naïve MSCs. Additionally, we showed that the delayed intranasal administration of IGF1-, LIF-, or IL11-hypersecreting MSCs, improved myelination and the functional outcome in EoP mice. In conclusion, the impaired migration and regenerative capacity of intranasally applied MSCs likely underlie the observed loss of efficacy after delayed treatment. The intranasal administration of IGF1-, LIF-, or IL11-hypersecreting MSCs, is a promising optimization strategy to prolong the window for effective MSC treatment in preterm infants with EoP.

Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.

Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.

Essentials of CAR-T Therapy and Associated Microbial Challenges in Long Run Immunotherapy.

Chimeric antigen receptor (CAR)-T cell therapy has shown potential in improving outcomes for individuals with hematological malignancies. However, achieving long-term full remission for blood cancer remains challenging due to severe life-threatening toxicities such as limited anti-tumor efficacy, antigen escape, trafficking restrictions, and limited tumor invasion. Furthermore, the interactions between CAR-T cells and their host tumor microenvironments have a significant impact on CAR-T function. To overcome these considerable hurdles, fresh methodologies and approaches are needed to produce more powerful CAR-T cells with greater anti-tumor activity and less toxicity. Despite advances in CAR-T research, microbial resistance remains a significant obstacle. In this review, we discuss and describe the basics of CAR-T structures, generations, challenges, and potential risks of infections in CAR-T cell therapy.

Therapeutic Characteristics of Alveolar-like Macrophages in Mouse Models of Hyperoxia and LPS-Induced Lung Inflammation.

Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving supplemental oxygen therapy; however, hyperoxia can induce pulmonary inflammation and cellular damage. Although alveolar macrophages (AMs) are essential for lung immune homeostasis, they become compromised during inflammatory lung injury. To combat this, stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using in vitro and in vivo approaches, we investigated the impact of hyperoxia on murine ALMs during acute inflammation. In vitro, ALMs retained their viability, growth and antimicrobial abilities when cultured at 60% O2,while they die at 90% O2. In contrast, ALMs instilled in mouse lungs remained viable during exposure of mice to 90% O2. The ability of the delivered ALMs to phagocytose Pseudomonas aeruginosa was not impaired by exposure to 60 or 90% O2. Furthermore, ALMs remained immunologically stable in a murine model of LPS-induced lung inflammation when exposed to 60 and 90% O2 and effectively attenuated the accumulation of CD11b+ inflammatory cells in the airways. These results support the potential use of ALMs in ARDS patients receiving supplemental oxygen therapy.

Facilitating the ethical sourcing of donor hematopoietic stem cells for cell and gene therapy research and development.

Aim: Unrelated stem cell donor registries (DRs) are increasingly engaging in the field of cell and gene therapy (CGT). This study aims to explore the values, concerns, needs and expectations of donors and members of the public on donating hematopoietic stem cells (HSCs) for CGT. Methods: Seven focus groups were conducted in 2019 with members of the public, prospective donors and donors on the Anthony Nolan DR in the UK. Results: Participants expressed concerns over increased frequency of donation and incidental findings and required more information on the type of research including the purpose and possible outcomes. Conclusion: Addressing donors' concerns, needs and expectations on donating cellular materials for CGT research and development is essential to maintaining the highest standards for donor care and safety within this rapidly emerging field.

This study aims to explore the values, concerns, needs and expectations of people who donate, or consider donating, their stem cells (cells that can develop into many different types of cells) for research that could lead to new medical treatments. We focused on the thoughts of these donors about providing their cells for use in cell and gene therapy (CGT) research, a field that is rapidly advancing but still forming its rules and ethical guidelines. In 2019, we conducted seven focus groups (FGs) with a total of 73 people in the UK. This included individuals who are registered as potential stem cell donors on the Anthony Nolan unrelated stem cell donor register (DR), those who have already donated stem cells and members of the general public. We explored their thoughts about their donated cells being used for research to develop new therapies rather than for direct treatment of patients. Questions during the FGs touched on topics such as the roles of various organizations in managing donated cells, the commercial use of these cells and where responsibilities lie in ensuring ethical practices. Participants expressed a strong desire for openness and clear communication regarding how their donated cells are used in research. They wanted to ensure that any use of their cells aligns with their personal values and the ethical standards of the organizations handling the donations. Participants expected DRs like Anthony Nolan to safeguard their interests and the ethical use of their cells. This study highlights that while donors are generally willing to contribute to advancements in CGT research, they need clear, understandable information about how their donations are used. This is crucial for maintaining their trust and willingness to donate. Overall, this study underscores the importance of ethical practices and donor engagement in the growing field of CGT, ensuring that donor contributions are respected and used responsibly.

Advances and challenges in regenerative therapies for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there is currently no effective agent to prevent aneurysm growth and rupture. Current treatment paradigms only rely on the identification and surveillance of small aneurysms, prior to ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues to address the degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, and pharmaceutical targets of AAA. Subsequently, a thorough discussion of regenerative approaches is provided. These include cellular approaches (vascular smooth muscle cells, endothelial cells, and mesenchymal stem cells) as well as the delivery of therapeutic molecules, gene therapies, and regenerative biomaterials. Lastly, additional barriers and considerations for clinical translation are provided. In conclusion, regenerative approaches hold significant promise for in situ reversal of tissue damages in AAA, necessitating sustained research and innovation to achieve successful and translatable therapies in a new era in AAA management.

Future directions in haploidentical hematopoietic stem cell transplantation.

Outcomes of haploidentical hematopoietic stem cell transplantation (haplo-SCT) have improved over time. Graft failure and graft-versus-host disease (GVHD), which were important complications in major human leukocyte antigen (HLA)-disparity stem cell transplantation, have significantly decreased. These improvements have led to an exponential increase in the use of haploidentical donors for transplantation, as well as in the number of publications evaluating haplo-SCT outcomes. Many studies focused on factors important in donor selection, novel conditioning regimens or GVHD prophylaxis, the impact of donor-specific anti-HLA antibodies (DSA), as well as strategies to prevent disease relapse post-transplant. DSA represents an important limitation and multimodality desensitization protocols, including plasma exchange, rituximab, intravenous immunoglobulin and donor buffy coat infusion, can contribute to the successful engraftment in patients with high DSA levels and is currently the standard therapy for highly allosensitized individuals. With regards to donor selection, younger donors are preferred due to lower risk of complications and better transplant outcomes. Moreover, recent studies also showed that younger haploidentical donors may be a better choice than older-matched unrelated donors. Improvement of disease relapse remains a top priority, and several studies have demonstrated that higher natural killer (NK) cell numbers early post-transplant are associated with improved outcomes. Prospective studies have started to assess the role of NK cell administration in decreasing post-transplant relapse. These studies suggest that the incorporation of other cell products post-transplant, including the administration of chimeric antigen receptor T-cells, should be explored in the future.

Lymphoma for the acute physician: diagnostic challenges and initial treatment decisions.

Prompt diagnosis of lymphoma facilitates early treatment and improves outcomes for patients. For non-haemato-oncologists, it is important to have an understanding of how lymphoma can present and the initial work-up. This review is intended to provide clinicians with background to aid clinical decisional making at presentation and when managing treatment related complications. There will be particular emphasis on emergency presentations (tumour lysis syndrome, management of patients with a mediastinal mass, infections in lymphoma patients) and novel treatment options which have unique toxicities often requiring multi-specialty expertise.

Nutritional Support Best Practices in Pediatric Blood and Marrow Transplant Patients: An Integrative Review.

Nutrition is vital to the long-term survival of children undergoing blood and marrow transplantation (BMT), but there is no standardization on how to optimize the nutritional status of these patients. A literature search was performed to evaluate nutritional support approaches currently in practice for pediatric patients who are undergoing BMT. CINAHL, Embase, and Cochrane databases were searched for peer-reviewed articles evaluating nutritional interventions for BMT recipients aged 20 or younger. Nine articles published between 2019 and 2023 were found and reviewed. The nutritional support varied between enteral nutrition, parenteral nutrition, a combination of both, and prophylactic feeding tube placement. The post-transplant outcomes identified as associated with alterations in nutritional regimens included length of stay, date of platelet engraftment, incidence of acute graft-versus-host disease, infection rate, and overall survival. The use of any amount of enteral nutrition compared to parenteral alone was beneficial. Complications during BMT can potentially be decreased via prioritizing enteral nutrition over parenteral. The paucity of literature on this topic highlights an unmet need in the field. Future research should focus on ways to optimize the nutritional support of transplant recipients, including increasing the likelihood of enteral feeding tube placement and utilization.

Cellular therapies for bone repair: current insights.

Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.

Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration.

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.

Chimeric Cell Therapies as a Novel Approach for Duchenne Muscular Dystrophy (DMD) and Muscle Regeneration.

Chimerism-based strategies represent a pioneering concept which has led to groundbreaking advancements in regenerative medicine and transplantation. This new approach offers therapeutic potential for the treatment of various diseases, including inherited disorders. The ongoing studies on chimeric cells prompted the development of Dystrophin-Expressing Chimeric (DEC) cells which were introduced as a potential therapy for Duchenne Muscular Dystrophy (DMD). DMD is a genetic condition that leads to premature death in adolescent boys and remains incurable with current methods. DEC therapy, created via the fusion of human myoblasts derived from normal and DMD-affected donors, has proven to be safe and efficacious when tested in experimental models of DMD after systemic-intraosseous administration. These studies confirmed increased dystrophin expression, which correlated with functional and morphological improvements in DMD-affected muscles, including cardiac, respiratory, and skeletal muscles. Furthermore, the application of DEC therapy in a clinical study confirmed its long-term safety and efficacy in DMD patients. This review summarizes the development of chimeric cell technology tested in preclinical models and clinical studies, highlighting the potential of DEC therapy in muscle regeneration and repair, and introduces chimeric cell-based therapies as a promising, novel approach for muscle regeneration and the treatment of DMD and other neuromuscular disorders.

Human Stem Cells in Regenerative Medicine.

Modern medicine now has the capacity to improve therapy for many human diseases by introducing adult somatic stem cells that can repair or replace defective or damaged tissues. However, the area is still in an early phase of development, so all new applications must be carefully designed for maximal safety as well as effectiveness.

Anti-inflammatory and immunomodulatory effects of mesenchymal stem cell therapy on parasitic drug resistance.

INTRODUCTION: The emergence of antiparasitic drug resistance poses a concerning threat to animals and humans. Mesenchymal Stem Cells (MSCs) have been widely used to treat infections in humans, pets, and livestock. Although this is an emerging field of study, the current review outlines possible mechanisms and examines potential synergism in combination therapies and the possible harmful effects of such an approach. AREAS COVERED: The present study delved into the latest pre-clinical research on utilizing MSCs to treat parasitic infections. As per investigations, the introduction of MSCs to patients grappling with parasitic diseases like schistosomiasis, malaria, cystic echinococcosis, toxoplasmosis, leishmaniasis, and trypanosomiasis has shown a reduction in parasite prevalence. This intervention also alters the levels of both pro- and anti-inflammatory cytokines. Furthermore, the combined administration of MSCs and antiparasitic drugs has demonstrated enhanced efficacy in combating parasites and modulating the immune response. EXPERT OPINION: Mesenchymal stem cells are a potential solution for addressing parasitic drug resistance. This is mainly because of their remarkable immunomodulatory abilities, which can potentially help combat parasites' resistance to drugs.

Phenotypic and Functional Characterization of Bovine Adipose-Derived Mesenchymal Stromal Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are increasingly trialed in cellular therapy applications in humans. They can also be applied to treat a range of diseases in animals, particularly in cattle to combat inflammatory conditions and aging-associated degenerative disorders. We sought to demonstrate the feasibility of obtaining MSCs from adipose tissue and characterizing them using established assays. METHODS: Bovine adipose MSCs (BvAdMSCs) were isolated using in-house optimized tissue digestion protocols and characterized by performing a colony formation assay, cell growth assessments, cell surface marker analysis by immunocytochemistry and flow cytometry, osteogenic and adipogenic differentiation, and secretion of indoleamine 2,3-dioxygenease (IDO). RESULTS: Our results demonstrate the feasibility of successful MSC isolation and culture expansion from bovine adipose tissues with characteristic features of colony formation, in vitro multilineage differentiation into osteogenic and adipogenic lineages, and cell surface marker expression of CD105, CD73, CD90, CD44, and CD166 with negative expression of CD45. BvAdMSCs secreted significant amounts of IDO with or without interferon-gamma stimulation, indicating ability for immunomodulation. CONCLUSIONS: We report a viable approach to obtaining autologous adipose-derived MSCs that can be applied as potential adjuvant cell therapy for tissue repair and regeneration in cattle. Our methodology can be utilized by veterinary cell therapy labs for preparing MSCs for disease management in cattle.

Mesenchymal stem cells in animal reproduction: sources, uses and scenario.

Studies regarding mesenchymal stem cells turned up in the 1960's and this cell type created a great number of questions about its functions and applicability in science and medicine. When used with therapeutic intent, these cells present an inclination to migrate to sites of injury, inflammation or disease, where they secrete bioactive factors that stimulates the synthesis of new tissue. In this context, studies using rodents reported that MSCs promoted positive effects in the ovarian function in mice with premature aging of follicular reserve. In female bovines, experimental stem cell-based therapies have been used to either generate new oocytes with in vitro quality or stimulate such action in vivo. It is also reported, that the intraovarian application of mesenchymal stem cells generates a greater production of embryos in vitro and the production of early and expanded blastocysts. Additionally, analysis of ovarian tissue in animal subjected to treatment showed an increase in the number of developing follicles. Nevertheless, the treatments involving stem cells with different modes of application, different sources and different species were able to act on the hormonal, tissue, cellular and metabolic levels, generating positive results in the recovery and improvement of ovarian functions.

Estudos sobre células-tronco mesenquimais surgiram na década de 1960 e esse tipo de célula gerou muitas dúvidas sobre suas funções e aplicabilidade na ciência e na medicina. Quando utilizadas com intuito terapêutico, essas células apresentam tendência a migrar para locais de lesão, inflamação ou doença, onde secretam fatores bioativos que estimulam a síntese de novos tecidos. Nesse contexto, estudos utilizando roedores relataram que as CTM promoveram efeitos positivos na função ovariana em camundongos com envelhecimento precoce da reserva folicular. Em fêmeas bovinas, terapias experimentais baseadas em células-tronco têm sido utilizadas para gerar novos oócitos com qualidade in vitro ou estimular tal ação in vivo. É relatado também que a aplicação intraovariana de células-tronco mesenquimais gera maior produção de embriões in vitro e produção de blastocistos precoces e expandidos. Além disso, a análise do tecido ovariano em animais submetidos ao tratamento mostrou aumento no número de folículos em desenvolvimento. Apesar disso, os tratamentos envolvendo células-tronco com diferentes modos de aplicação, diferentes fontes e diferentes espécies foram capazes de atuar nos níveis hormonal, tecidual, celular e metabólico, gerando resultados positivos na recuperação e melhora das funções ovarianas.

Imaging CAR-NK cells targeted to HER2 ovarian cancer with human sodium-iodide symporter-based positron emission tomography.

Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model.NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([18F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells.Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.

Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models.

Background: Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion. Objective: To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment. Methods: dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed. Results: Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin ß1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs. Conclusion: We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.

Highlight of 2023: CAR T cells driving precision therapy for autoimmune disease.

CAR T cell therapy is showing remarkable results in autoimmune disease with treatment-refractory patients showing durable drug-free remission. Here, we highlight five key papers from 2023 that are driving the development of CAR T cells to improve precision, safety, efficacy and accessibility for the treatment of autoantibody-associated autoimmune diseases.