From the pioneering days of cell therapy to the achievement of bioprinting organs, tissue engineering, and regenerative medicine have seen tremendous technological advancements, offering solutions for restoring damaged tissues and organs. However, only a few products and technologies have received United States Food and Drug Administration approval. This review highlights significant progress in cell therapy, extracellular vesicle-based therapy, and tissue engineering. Hematopoietic stem cell transplantation is a powerful tool for treating many diseases, especially hematological malignancies. Mesenchymal stem cells have been extensively studied. The discovery of induced pluripotent stem cells has revolutionized disease modeling and regenerative applications, paving the way for personalized medicine. Gene therapy represents an innovative approach to the treatment of genetic disorders. Additionally, extracellular vesicle-based therapies have emerged as rising stars, offering promising solutions in diagnostics, cell-free therapeutics, drug delivery, and targeted therapy. Advances in tissue engineering enable complex tissue constructs, further transforming the field. Despite these advancements, many technical, ethical, and regulatory challenges remain. This review addresses the current bottlenecks, emphasizing novel technologies and interdisciplinary research to overcome these hurdles. Standardizing practices and conducting clinical trials will balance innovation and regulation, improving patient outcomes and quality of life.

The development of chimeric antigen receptor (CAR) T-cells, engineered from peripheral T-lymphocytes of a patient with lymphoma, in order to specifically target tumor cells, has been a revolution in adoptive cell therapy (ACT). As outlined in this review, ACT was initiated by hematopoietic cell transplantation (HSCT) and re-injection of interleukin-boosted tumor-infiltrating lymphocytes (TIL). The innovative venture of genetically modifying autologous peripheral T-cells to target them to cell-surface tumoral antigens through an antibody-derived structure (i.e. independent of major histocompatibility antigen presentation, physiologically necessary for T-cell activation), and intracytoplasmic T-cell costimulatory peptides, via a novel membrane CAR, has been an outstanding breakthrough. Here, focusing on B-cell hematological malignancies and mostly non-Hodgkin lymphoma, attention is brought to the importance of providing an optimal microenvironment for such therapeutic cells to proliferate and positively develop anti-tumoral cytotoxicity. This, perhaps paradoxically, implies a pre-infusion step of deep lymphopenia and deregulation of immunosuppressive mechanisms enhanced by tumoral cells. Fludarabine and cyclophosphamide appear to be the most efficient lymphodepletive drugs in this context, dosage being of importance, as will be illustrated by a thorough literature review.

The role of ABO blood group system mismatch on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes is controversial since current publications of large datasets are lacking. We retrospectively analyzed 30,487 patients transplanted between 2010 and 2021 using the EBMT registry to assess ABO incompatibility's effect on non-relapse mortality (NRM), overall survival (OS), progression-free survival (PFS), relapse incidence (RI), acute GvHD (aGvHD), chronic GvHD (cGvHD), and neutrophil engraftment. Transplantations were classified as ABO-compatible (56.3%), major (18.1%), minor (20.1%), and bidirectional (5.5%) incompatibilities. Mainly peripheral blood stem cells (PBSC) were used as the cell source in 85.6% of cases. Multivariate analysis found no significant association between compatibility status, with the compatible group serving as the reference, and NRM, OS, PFS, RI or cGvHD. The incidence of non-engraftment was significantly higher in the major (HR 1.04, 95% CI 1.01-1.07, p = 0.021) and bidirectional (HR 1.09, 95% CI 1.03-1.15, p = 0.003) incompatibilities. At the same time, the risk of severe aGvHD grades III-IV was lower in the major incompatibility group (HR 0.85, 95% CI 0.77-0.94, p = 0.001). Our large contemporary study, showing no major impact on outcomes, suggests that the ABO blood group system should not be a primary consideration in donor selection for PBSC-based allo-HCT.

Kidney injury encompasses a broad spectrum of structural and functional abnormalities, directly associated with stem cell transplantation. Acute kidney injury and chronic kidney disease represent perilous complications of hematopoietic stem cell transplantation (HSCT), with an elevated risk of mortality and progression to end-stage renal disease. The early detection of these complications is, therefore, paramount, and research is increasingly focused on the identification of novel biomarkers of kidney damage. Recently, proenkephalin (PENK), a monomeric peptide that is freely filtered by the glomerulus and thus reflects glomerular filtration very well, has been shown to be an additional useful predictor of the occurrence of acute kidney injury and heart failure. Dickkopf-3 (DKK3) is a glycoprotein secreted by the renal tubular epithelium in response to stress and has been implicated in the development of interstitial fibrosis. It has therefore been evaluated primarily as a marker of fibrosis in chronic kidney disease (CKD), but may also help predict the development of acute kiney injury. Uromodulin is regarded as a renal marker. Previous studies have examined the potential of PENK, DKK-3 and uromodulin as a biomarker in individuals with preserved renal function. However, the urinary levels of PENK, DKK-3 and uromodulin in patients following HSCT have not yet been established. The objective of the present study was to assess urinary PENK, DKK-3, and uromodulin concentrations in patients who had been under ambulatory care of the Hematology, Transplantation and Internal Medicine Department for a minimum of three months following HSCT, and to investigate their correlations with kidney function, as reflected by serum creatinine and eGFR. The study population comprised 80 patients who had undergone allogeneic HSCT for various reasons, primarily hematological malignancies such as acute leukemias and lymphomas. In addition, 32 healthy volunteers were included in order to establish normal ranges for the biomarkers of interest. Urine concentrations of proenkephalin, DKK-3, and uromodulin were evaluated using a commercially available sandwich ELISA immunoassay. Demographic and clinical data were retrieved from the patients' records. Statistical analyses were conducted using XLSLAT 2022 (Lumivero, Denver, CO, USA) and STATISTICAv13.0 (StatSoft, Tulsa, OH, USA). The results showed that PENK and DKK-3 levels were significantly higher in patients after HSCT compared to healthy volunteers. Furthermore, when patients were divided according to kidney function (below and over 60 mL/min/1.72 m2), it was found that the concentration of PENK and DKK-3 were significantly higher in 23 patients with CKD stage 3 relative to patients with eGFR over 60 mL min 1.72 m2. In univariate correlations, PENK demonstrated an inverse relationship with eGFR (r: -0.21, p < 0.05), while DKK-3 exhibited no significant correlation with creatinine or eGFR.Patients following allogeneic HSCT, despite having normal or near-normal kidney function, exhibited evidence of kidney injury. However, further research is necessary to ascertain the clinical utility of the novel biomarker.

Since the first approval of an immune checkpoint inhibitor, we have witnessed the clinical success of cancer immunotherapy. Adoptive T-cell therapy with chimeric antigen receptor T (CAR-T) cells has shown remarkable efficacy in hematological malignancies. Concurrently with these successes, the cancer immunoediting concept that refined the cancer immunosurveillance concept underpinned the scientific mechanism and reason for past failures, as well as recent breakthroughs in cancer immunotherapy. Now, we face the next step of issues to be solved in this field, such as tumor heterogeneity, the tumor microenvironment, the metabolism of tumors and the immune system, and personalized approaches for patients, aiming to expand the population benefitted by the therapies.

Immune-mediated disorders are a broad range of diseases, arising as consequence of immune defects, exaggerated/misguided immune response or a mixture of both conditions. Their frequency is on a rise in the developed societies and they pose a significant challenge for diagnosis and treatment. Traditional pharmacological, monoclonal antibody-based or polyclonal antibody replacement-based therapies aiming at modulation of the immune responses give very often dissatisfactory results and/or are burdened with unacceptable adverse effects. In recent years, a new group of treatment modalities has emerged, utilizing cells as living drugs, especially with the use of the up-to-date genetic engineering. These modern cellular therapies are designed to offer a high potential for more targeted, safe, durable, and personalized treatment options. This work briefly reviews the latest advances in the treatment of immune-mediated disorders, mainly those related to exaggeration of the immune response, with such cellular therapies as hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), regulatory T cells (Tregs), chimeric antigen receptor (CAR) T cells and others. We highlight the main features of these therapies as new treatment options for taming the dysregulated immune system. Undoubtfully, in near future such therapies can provide lasting remissions in a range of immune-mediated disorders with reduced treatment burden and improved quality of life for the patients.

Hematopoietic stem cell transplantation (HSCT) emerged over sixty years ago as a groundbreaking and potentially curative treatment for patients with acute myeloid leukemia (AML) who were not responding to chemotherapy. In this study, we aimed to investigate prognostic factors for survival after allo-HSCT in AML patients. This retrospective cohort study was carried out using data from 742 adult AML patients underwent allo-HSCT. we analysis prognostic factors for survival after allo-HSCT with censored quantile regression model. The 5-year OS, DFS and GRFS rates were 58, 53, and 30%, respectively. OS for recipients older than 35 years was 0.95 and 1.12 years lower than that for recipients under 35 years in the 25th and 40th percentiles, respectively. Compared to patients in their CRІ, those with CRІІІ disease experienced a decrease in OS at the 25th and 40th percentiles by 1.72 and 3.72 years, respectively. Moreover, OS for ABO matched patients was 0.92 and 1.29 years longer than that of patients with an ABO major mismatch. This study could assist oncologists and hematologists in understanding the prognostic factors affecting patient survival across various survival ranges, thereby potentially extending patients' lifespans.

Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery. Here, we uncovered the spatiotemporal dynamics of early active hematopoiesis, "hematopoietic cell inflation," using a highly sensitive in vivo imaging system. Hematopoietic cell inflation occurs in three peaks in the spleen after transplantation, with common myeloid progenitors (CMPs), notably characterized by HSC-like signatures, playing a central role. Leveraging these findings, we developed expanded CMPs (exCMPs), which exhibit a gene expression pattern that selectively proliferates in the spleen and promotes hematopoietic expansion. Moreover, universal exCMPs supported early hematopoiesis in allogeneic transplantation. Human universal exCMPs have the potential to be a viable therapeutic enhancement for all HSC transplant patients.

Background/Objectives: We aimed to identify the molecular signatures of primitive CD34+ and CD34- hematopoietic stem/progenitor cell (HSC/HPC) subsets in cord blood and bone marrow samples. Methods: CD34+ and CD34- HSC/HPC subsets from cord blood and bone marrow were characterized using flow cytometry, real-time PCR, and proteomic analysis to evaluate their phenotypic and molecular profiles. Results: Our findings revealed a significantly higher percentage of Lin-CD34-CD38Low/- (-/-) cells than of Lin-CD34+CD38Low/- (+/-) cells in cord blood. Aldehyde dehydrogenase levels were significantly lower in (-/-) than in (+/-) cells. Clonogenic ability was lower in (-/-) than in (+/-) cells. However, CD34- cells exhibited potent megakaryocyte/erythrocyte differentiation ability. Importantly, the HSC/HPC subsets expressed pluripotency or stemness genes (SOX2, Nanog, and OCT4); however, OCT4 expression significantly increased in (-/-) compared with (+/-) cells. We identified 304 proteins in the HSC/HPC subsets-85.6% had similar expression patterns in the two subsets; only 14.4% were differentially expressed between (-/-) and (+/-) cells. This implies their comparability at the protein level. Certain proteins were implicated in cellular-development-, gene-expression-, and embryonic-development-related signaling networks. Conclusions: Distinct biological and functional characteristics were observed between (-/-) and (+/-) HSC/HPC subsets. Some of the identified proteins may be novel HSC/HPC subsets markers for clinical applications after validation.

Hematopoietic stem cell transplantation (HSCT) is a promising approach in regenerative medicine and serves as a standard treatment for different malignant and non-malignant conditions. Despite its widespread applications, HSCT is associated with various complications that compromise patients' lives and pose considerable risks of morbidity and mortality. Understanding the molecular physiology of HSCs is fundamental to ultimately enhance the mobilization, engraftment and differentiation of HSCs, thus unleashing the full therapeutic potential of HSCT in the treated patients. This review outlines the current understanding of HSC biology and its relevance to the clinical challenges associated with HSCT. Furthermore, we critically discuss the pros and cons of the preclinical murine models exploited in the HSCT field. Understanding the molecular physiology of HSCs will ultimately unleash the full therapeutic potential of HSCT. HSCs derived from induced pluripotent stem cells (iPSCs) might present an attractive tool which could be exploited preclinically and clinically. Nonetheless, further studies are warranted to systematically evaluate their potential in terms of improving the therapeutic outcome and minimizing the adverse effects of HSCT.

This report describes the case of a 29-year-old patient with chronic myeloid leukemia in the blast phase who underwent hematopoietic stem cell transplantation (HSCT) after living-donor liver transplantation. Donor selection, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis are discussed. The patient received a non-myeloablative conditioning regimen and ABO blood group-matched unrelated human leukocyte antigen fully-matched donors. Immunosuppressants tacrolimus and mycophenolate mofetil were administered to prevent GVHD. Maintenance therapy with ponatinib effectively maintained remission. This case highlights the complexities of managing HSCT after solid organ transplantation and suggests strategies for future cases.

Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment. ScRNA-seq allows the identification of quiescent stem-like cells, and leukemia stem cells responsible for resistance to therapeutic approaches and relapse after treatment. This method also introduces the factors and mechanisms that enhance the efficacy of the HSCT process. Generated data of the transcriptional profile of the AML could even allow the development of cancer vaccines and CAR T-cell therapies while saving valuable time and alleviating dangerous side effects of chemotherapy and HSCT in vivo. However, scRNA-seq applications face various challenges such as a large amount of data for high-dimensional analysis, technical noise, batch effects, and finding small biological patterns, which could be improved in combination with artificial intelligence models.

The use of stem cell therapy is a rapidly evolving and progressing frontier of science that has been used to treat illnesses such as malignancies, immunodeficiencies, and metabolic syndromes. This review aims to give an overview of the use of stem cell therapy in the treatment of pain caused by diabetic neuropathy, osteoarthritis, and other spinal cord pathologies.

Pain is defined as a generalized or localized feeling of distress related to a physical or emotional stimulus and can be caused by a multitude of pathologies. The field of pain management has explored many strategies such as gene therapies, neuromodulation, platelet-rich plasma, and numerous pharmacotherapies. The approach to the delivery of these strategies has varied, with the method of stem cell therapy delivery being the focus of this present investigation. In addition, we combined several different studies to analyze the effects of stem cell therapies and improvement in pain scores quantified by the visual analog scale (VAS). The overall results showed a mean difference of -2.58, suggesting that the stem cell treatment group had a lower VAS score at 6 months compared to the control group. The use of different types of stem cells, such as pluripotent and mesenchymal stem cells, play a critical role in the care of cases suffering from pain. Effective delivery methods are evolving and can transform treatment options in the future, for which large cohort studies are warranted.

Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent cells with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (1011-1012) of new cells generated daily in a healthy young human adult are of hematopoietic origin. Therapeutically, human HSCs have contributed to over 1.5 million hematopoietic cell transplants (HCTs) globally, making this the most successful regenerative therapy to date. We will commence this review by briefly highlighting selected key achievements (from 1868 to the end of the 20th century) that have contributed to this accomplishment. Much of our knowledge of hematopoiesis is based on small animal models that, despite their enormous importance, do not always recapitulate human hematopoiesis. Given this, we will critically review the progress and challenges faced in identifying adult human HSCs and tracing their lineage differentiation trajectories, referring to murine studies as needed. Moving forward and given that human hematopoiesis is dynamic and can readily adjust to a variety of stressors, we will then discuss recent research advances contributing to understanding (i) which HSPCs maintain daily steady state human hematopoiesis, (ii) where these are located, and (iii) which mechanisms come into play when homeostatic hematopoiesis switches to stress-induced or emergency hematopoiesis.

For patients with leukemia and other hematological malignancies, allogeneic hematopoietic stem cell transplantation (allo-SCT) represents a primary treatment option. This therapy involves the transplantation of healthy stem cells from a compatible donor into a preconditioned recipient. These transplanted cells then recognize and attack the remaining leukemia cells or other malignant cells in the recipient, a process named graft-versus-leukemia (GVL) immunity. This immunological response contributes to the therapeutic effect of the transplant, reducing the risk of disease relapse or progression. However, it can also lead to graft-versus-host disease (GVHD), the main complication related to allo-SCT. Therefore, effective treatment requires a balance between GVL immunity and GVHD. This chapter describes protocols for studying GVL immunity in allogeneic and humanized (xenogeneic) mouse models, including the challenges and strategies encountered in the induction of GVL immunity in such models.

Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

Hematopoietic stem cells (HSCs) are an ideal source for the treatment of many hematological diseases and malignancies, as well as diseases of other systems, because of their two important features, self-renewal and multipotential differentiation, which have the ability to rebuild the blood system and immune system of the body. However, so far, the insufficient number of available HSCs, whether from bone marrow (BM), mobilized peripheral blood or umbilical cord blood, is still the main restricting factor for the clinical application. Therefore, strategies to expand HSCs numbers and maintain HSCs functions through ex vivo culture are urgently required. In this review, we outline the basic biology characteristics of HSCs, and focus on the regulatory factors in BM niche affecting the functions of HSCs. Then, we introduce several representative strategies used for HSCs from these three sources ex vivo expansion associated with BM niche. These findings have deepened our understanding of the mechanisms by which HSCs balance self-renewal and differentiation and provided a theoretical basis for the efficient clinical HSCs expansion.

Stem cells are the foundation for cell therapy due to their ability to self-renew, differentiate into other cell types, and persist throughout the life of an organism. Stem cell isolation and transplantation have not yet been established in Hexacorallia, a cnidarian subclass containing stony corals and sea anemones. Here, we demonstrate that candidate stem cells in the hexacorallian Nematostella vectensis can be transplanted into adult animals. These cells exhibited the hallmarks of stem cell functional properties; they integrated into recipients' tissues and rescued them from lethal doses of chemotherapy. Additionally, these cells proliferated and survived serial transplantations. Notably, we showed that this cellular subpopulation can be enriched by sorting using species-non-specific cell markers and that similar subpopulations of cells can be isolated from other hexacorallians, including stony corals. This research establishes the basis for studying stem cell biology on a functional level in Hexacorallia.

Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the nasopharynx and is consistently associated with the Epstein-Barr virus (EBV) infection. Its unique anatomical location and complex aetiology often result in advanced-stage disease at first diagnosis. While radiotherapy (RT) and chemotherapy have been the mainstays of treatment, they often fail to prevent tumour recurrence and metastasis, leading to high rates of treatment failure and mortality. Recent advancement in cell-based therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown great promise in hematological malignancies and are now being investigated for NPC. However, challenges such as targeting specific tumour antigens, limited T cell persistence and proliferation, and managing treatment-related toxicities must be addressed. Extensive research is needed to enhance the effectiveness and safety of these therapies, paving the way for their integration into standard clinical practice for better management of NPC and a better quality of life for human health.

Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare lysosomal storage disorders caused by deficient acid ceramidase (ACDase) activity. Although both conditions are caused by mutations in the ASAH1 gene, clinical presentations differ considerably. FD patients usually die in childhood, while SMA-PME patients can live until adulthood. There is no treatment for FD or SMA-PME. Hematopoietic stem cell transplantation (HSCT) and gene therapy strategies for the treatment of ACDase deficiency are being investigated. We have previously generated and characterized mouse models of both FD and SMA-PME that recapitulate the symptoms described in patients. Here, we show that HSCT improves lifespan, behavior, hematopoietic system anomalies, and plasma cytokine levels and significantly reduces histiocytic infiltration and ceramide accumulation throughout the tissues investigated, including the CNS, in both models of ACDase-deficient mice. HSCT was also successful in preventing lesion development and significant demyelination of the spinal cord seen in SMA-PME mice. Importantly, we note that only early and generally pre-symptomatic treatment was effective, and kidney impairment was not improved in either model.

The combination of cord blood transplant with progenitor cells from partially HLA-matched adult donors (haplo-cord transplant) has been used over the past two decades. In Europe and the US the adult donor graft is CD34 selected and provides early hematopoiesis, but durable engraftment derives from the cord blood graft (CD34 selected haplo-cord). Neutrophil recovery is prompt and rates of acute and chronic GVHD are low. Recent Chinese studies combine cord blood grafts with T-replete haplo-identical grafts (unmodified haplo-cord). The haplo graft usually establishes dominance and UCB chimerism is rarely detected. Comparison studies suggest considerably decreased rates of relapse and improved outcomes, compared with either haplo-identical transplant or CBU transplant, particularly in patients with advanced leukemia. A recent prospective randomized study confirms this. Haplo-cord mitigates the engraftment delay of UCB transplant. The unique biology of UCB grafts results in low GVHD and improved GVL especially beneficial in high-risk disease.

Tissue stem cells (TSCs), which reside in specialized tissues, constitute the major cell sources for tissue homeostasis and regeneration, and the contribution of transcriptional or epigenetic regulation of distinct biological processes in TSCs has been discussed in the past few decades. Meanwhile, ATP-dependent chromatin remodelers use the energy from ATP hydrolysis to remodel nucleosomes, thereby affecting chromatin dynamics and the regulation of gene expression programs in each cell type. However, the role of chromatin remodelers in tissue stem cell fate determination is less well understood. In this review, we systematically discuss recent advances in epigenetic control by chromatin remodelers of hematopoietic stem cells, intestinal epithelial stem cells, neural stem cells, and skin stem cells in their fate determination and highlight the importance of their essential role in tissue homeostasis, development, and regeneration. Moreover, the exploration of the molecular and cellular mechanisms of TSCs is crucial for advancing our understanding of tissue maintenance and for the discovery of novel therapeutic targets.

Bone marrow cellular therapy has undergone a remarkable evolution, significantly impacting the treatment of musculoskeletal disorders. This review traces the historical trajectory from early mythological references to contemporary scientific advancements. The groundbreaking work of Friedenstein in 1968, identifying fibroblast colony-forming cells in bone marrow, laid the foundation for future studies. Caplan's subsequent identification of mesenchymal stem cells (MSCs) in 1991 highlighted their differentiation potential and immunomodulatory properties, establishing them as key players in regenerative medicine. Contemporary research has focused on refining techniques for isolating and applying bone marrow-derived MSCs. These cells have shown promise in treating conditions like osteonecrosis, osteoarthritis, and tendon injuries thanks to their ability to promote tissue repair, modulate immune responses, and enhance angiogenesis. Clinical studies have demonstrated significant improvements in pain relief, functional recovery, and tissue regeneration. Innovations such as the ACH classification system and advancements in bone marrow aspiration methods have standardized practices, improving the consistency and efficacy of these therapies. Recent clinical trials have validated the therapeutic potential of bone marrow-derived products, highlighting their advantages in both surgical and non-surgical applications. Studies have shown that MSCs can reduce inflammation, support bone healing, and enhance cartilage repair. However, challenges remain, including the need for rigorous characterization of cell populations and standardized reporting in clinical trials. Addressing these issues is crucial for advancing the field and ensuring the reliable application of these therapies. Looking ahead, future research should focus on integrating bone marrow-derived products with other regenerative techniques and exploring non-surgical interventions. The continued innovation and refinement of these therapies hold promise for revolutionizing the treatment of musculoskeletal disorders, offering improved patient outcomes, and advancing the boundaries of medical science.

Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial.

The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of "disagree" or "abstain", they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved.

Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies.

In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose-response associations, and comparative analysis between different injectable biologics.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

The use of hematopoietic cell transplantation (HCT) has expanded in the last 4 decades to include an older and more comorbid population. These patients face an increased risk of cardiovascular disease after HCT. The risk varies depending on several factors, including the type of transplant (autologous or allogeneic). Many therapies used in HCT have the potential to be cardiotoxic. Cardiovascular complications after HCT include atrial arrhythmias, heart failure, myocardial infarction, and pericardial effusions. Before HCT, patients should undergo a comprehensive cardiovascular assessment, with ongoing surveillance tailored to their individual level of cardiovascular risk. In this review, we provide an overview of cardiotoxicity after HCT and outline our approach to risk assessment and ongoing care.

Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM.

We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT in MM patients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted meta-analysis in the NDMM/frontline setting and RRMM/salvage setting independently.

The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively.

Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/ frontline setting.

Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients.

Pluripotent stem cells are defined as cells that can generate cells of lineages from all three germ layers, ectoderm, mesoderm, and endoderm. On the contrary, unipotent and multipotent stem cells develop into one or more cell types respectively, but their differentiation is limited to the cells present in the tissue of origin or, at most, from the same germ layer. Multipotent and unipotent stem cells have been isolated from a variety of adult tissues, Instead, the presence in adult tissues of pluripotent stem cells is a very debated issue. In the early embryos, all cells are pluripotent. In mammalians, after birth, pluripotent cells are maintained in the bone-marrow and possibly in gonads. In fact, pluripotent cells were isolated from marrow aspirates and cord blood and from cultured bone-marrow stromal cells (MSCs). Only in few cases, pluripotent cells were isolated from other tissues. In addition to have the potential to differentiate toward lineages derived from all three germ layers, the isolated pluripotent cells shared other properties, including the expression of cell surface stage specific embryonic antigen (SSEA) and of transcription factors active in the early embryos, but they were variously described and named. However, it is likely that they are part of the same cell population and that observed diversities were the results of different isolation and expansion strategies. Adult pluripotent stem cells are quiescent and self-renew at very low rate. They are maintained in that state under the influence of the "niche" inside which they are located. Any tissue damage causes the release in the blood of inflammatory cytokines and molecules that activate the stem cells and their mobilization and homing in the injured tissue. The inflammatory response could also determine the dedifferentiation of mature cells and their reversion to a progenitor stage and at the same time stimulate the progenitors to proliferate and differentiate to replace the damaged cells. In this review we rate articles reporting isolation and characterization of tissue resident pluripotent cells. In the attempt to reconcile observations made by different authors, we propose a unifying picture that could represent a starting point for future experiments.

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are gaining significant attention in regenerative medicine for their potential to treat degenerative diseases and mitigate radiation injuries. WJ-MSCs are more naïve and have a better safety profile, making them suitable for both autologous and allogeneic transplantations. This review highlights the regenerative potential of WJ-MSCs and their clinical applications in mitigating various types of radiation injuries. In this review, we will also describe why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine along with a balanced view on their strengths and weaknesses. Finally, the most updated literature related to both preclinical and clinical usage of WJ-MSCs for their potential application in the regeneration of tissues and organs will also be compiled.

Advancements in cardiovascular (CV) disease management are notable, yet health inequities prevail, associated with increased morbidity and mortality noted among non-Hispanic African Americans in the United States. The 2002 Institute of Medicine Report revealed ongoing racial and ethnic health care disparities, spearheading a deeper understanding of the social determinants of health and systemic racism to develop strategies for CV health equity (HE). This article outlines the strategic HE approach of the American College of Cardiology, comprising 6 strategic equity domains: workforce pathway inclusivity, health care, data, science, and tools; education and training; membership, partnership, and collaboration; advocacy and policy; and clinical trial diversity. The American College of Cardiology's Health Equity Task Force champions the improvement of patients' lived experiences, population health, and clinician well-being while reducing health care costs-the Quadruple Aim of Health Equity. Thus, we examine multifaceted HE interventions and provide evidence for scalable real-world interventions to promote equitable CV care.

With the long persistence of complex, chronic diseases in society, there is increasing motivation to develop cells as living medicine to treat diseases ranging from cancer to wounds. While cell therapies can significantly impact healthcare, the shortage of starter cells meant that considerable raw materials must be channeled solely for cell expansion, leading to expensive products with long manufacturing time which can prevent accessibility by patients who either cannot afford the treatment or have highly aggressive diseases and cannot wait that long. Over the last three decades, there has been increasing knowledge on the effects of electrical modulation on proliferation, but to the best of the knowledge, none of these studies went beyond how electro-control of cell proliferation may be extended to enhance industrial scale cell manufacturing. Here, this review is started by discussing the importance of maximizing cell yield during manufacturing before comparing strategies spanning biomolecular/chemical/physical to modulate cell proliferation. Next, the authors describe how factors governing invasive and non-invasive electrical stimulation (ES) including capacitive coupling electric field may be modified to boost cell manufacturing. This review concludes by describing what needs to be urgently performed to bridge the gap between academic investigation of ES to industrial applications.

The anterior chamber of the eye (ACE) is distinct in its anatomy, optics, and immunology. This guarantees that the eye perceives visual information in the context of physiology even when encountering adverse incidents like inflammation. In addition, this endows the ACE with the special nursery bed iris enriched in vasculatures and nerves. The ACE constitutes a confined space enclosing an oxygen/nutrient-rich, immune-privileged, and less stressful milieu as well as an optically transparent medium. Therefore, aside from visual perception, the ACE unexpectedly serves as an excellent transplantation site for different body parts and a unique platform for noninvasive, longitudinal, and intravital microimaging of different grafts. On the basis of these merits, the ACE technology has evolved from the prototypical through the conventional to the advanced version. Studies using this technology as a versatile biomedical research platform have led to a diverse range of basic knowledge and in-depth understanding of a variety of cells, tissues, and organs as well as artificial biomaterials, pharmaceuticals, and abiotic substances. Remarkably, the technology turns in vivo dynamic imaging of the morphological characteristics, organotypic features, developmental fates, and specific functions of intracameral grafts into reality under physiological and pathological conditions. Here we review the anatomical, optical, and immunological bases as well as technical details of the ACE technology. Moreover, we discuss major achievements obtained and potential prospective avenues for this technology.

Stem cell apheresis in the context of autologous stem cell transplantation requires an accurate cluster of differentiantion 34 (CD34+) count determined by flow cytometry as the current gold standard. Since flow cytometry is a personnel and time-intensive diagnostic tool, automated stem cell enumeration may provide a promising alternative. Hence, this study aimed to compare automated hematopoietic progenitor enumeration carried out on a Sysmex XN-20 module compared with conventional flow cytometric measurements.

One hundred forty-three blood samples from 41 patients were included in this study. Correlation between the two methods was calculated over all samples, depending on leukocyte count and diagnosis.

Overall, we found a high degree of correlation (r = 0.884). Furthermore, correlation was not impaired by elevated leukocyte counts (>10 000/μL, r = 0.860 vs <10 000/μL, r = 0.849; >20 000/μL, r = 0.843 vs <20 000/μL, r = 0.875). However, correlation was significantly impaired in patients with multiple myeloma (multiple myeloma r = 0.840 vs nonmyeloma r = 0.934).

Stem cell measurement carried out on the Sysmex XN-20 module provides a significant correlation with flow cytometry and might be implemented in clinical practice. In clinical decision-making, there was discrepancy of under 15% of cases. In multiple myeloma patients, XN-20 should be used with caution.

Hematopoietic cell transplantation (HCT) was developed more than 65 years ago to treat malignant blood disorders and irreversible bone marrow failures, with the aim of replacing a diseased hematopoietic system with a healthy one (allogeneic HCT). Decades later, the procedure was adapted to apply maximal chemotherapy or radiotherapy, which would result in bone marrow failure, but could be remedied by an infusion of a patient's own cryopreserved bone marrow (autologous HCT). Both treatments are high-risk and complex, especially during the initial phases. However, concerted efforts, vision, and collaboration between physicians and centers worldwide have resulted in HCT becoming a standard of care for many hematological disorders with progressive improvements in outcomes. Registries and the collaboration of societies worldwide have enabled the delivery of this curative therapy to many patients with fatal hematological diseases. More than 1.5 million HCT were performed between 1957 and 2019, and activity is continuously increasing worldwide.