Efficacy Of Stem Cell Transplantation Research Articles

Near-infrared-II fluorescence/magnetic resonance double modal imaging of transplanted stem cells using lanthanide co-doped gadolinium oxide nanoparticles.

To ensure maximum therapeutic safety and efficacy of stem cell transplantation, it is essential to observe the kinetics of behavior, accumulation, and engraftment of transplanted stem cells in vivo. However, it is difficult to detect transplanted stem cells with high sensitivity by conventional in vivo imaging technologies. To diagnose the kinetics of transplanted stem cells, we prepared multifunctional nanoparticles, Gd2O3 co-doped with Er3+ and Yb3+ (Gd2O3: Er, Yb-NPs), and developed an in vivo double modal imaging technique with near-infrared-II (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI) of stem cells using Gd2O3: Er, Yb-NPs. Gd2O3: Er, Yb-NPs were transduced into adipose tissue-derived stem cells (ASCs) through a simple incubation process without cytotoxicity under certain concentrations of Gd2O3: Er, Yb-NPs and were found not to affect the morphology of ASCs. ASCs labeled with Gd2O3: Er, Yb-NPs were transplanted subcutaneously onto the backs of mice, and successfully imaged with good contrast using an in vivo NIR-II fluorescence imaging and MRI system. These data suggest that Gd2O3: Er, Yb-NPs may be useful for in vivo double modal imaging with NIR-II fluorescence imaging and MRI of transplanted stem cells.

Abstract TP42: Single Stem Cell Modification With Biomaterials and Oligopeptide for Stroke Targeting and Recovery

Stem cell transplantation enhances stroke recovery. A primary mechanism is the release of trophic factors, such as VEGF, BDNF, and CNTF, which are thought to stimulate brain plasticity and recovery mechanisms. While promising, the treatment efficacy of stem cell transplantation is restricted by inadequate stem cell survival and insufficient trophic factor release at the stroke site. To address this, we have developed a single stem cell encapsulation method (SingleStem) using the naturally occurring glycolysis process and click chemistry strategy to modify individual neural progenitor cells (NPCs) with polymeric materials and the stroke targeting oligopeptide (E-selectin binding oligopeptide (Esbp)). Our data demonstrate that the polymeric biomaterial coating provided uniform cell protection and control of individual NPC, which increased transplanted NPC survival and enabled trophic factor release modulation (such as VEGFA and VEGFB). Additionally, the stroke targeting oligopeptide Esbp is able to bind to components on activated endothelial cells to facilitated NPC homing to the stroke region and improve stroke recovery efficacy. These advantages enable SingleStem to be an effective stroke recovery tool to improve stem cell efficacy and understand stroke recovery mechanisms.

Current Status and Progress in Stem Cell Therapy for Intracerebral Hemorrhage.

Intracerebral hemorrhage is a highly prevalent and prognostically poor disease, imposing immeasurable harm on human life and health. However, the treatment options for intracerebral hemorrhage are severely limited, particularly in terms of improving the microenvironment of the lesion, promoting neuronal cell survival, and enhancing neural function. This review comprehensively discussed the application of stem cell therapy for intracerebral hemorrhage, providing a systematic summary of its developmental history, types of transplants, transplantation routes, and transplantation timing. Moreover, this review presented the latest research progress in enhancing the efficacy of stem cell transplantation, including pretransplantation preconditioning, genetic modification, combined therapy, and other diverse strategies. Furthermore, this review pioneeringly elaborated on the barriers to clinical translation for stem cell therapy. These discussions were of significant importance for promoting stem cell therapy for intracerebral hemorrhage, facilitating its clinical translation, and improving patient prognosis.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Effects of Timing on the Efficacy of Stem Cell Transplantation after Acute Myocardial Infarction

Acute myocardial infarction (AMI) is the blocking of coronary arteries that prevents oxygenated blood from reaching the heart tissues, resulting in damage to the myocardium and affecting heart function. This condition affects millions of people every year and is detrimental to their quality of life. Several clinical trials have investigated the efficacy of using bone marrow-derived stem cells (BMSCs) to improve heart function after AMIs. However, different variables could impact the results of the trials, one of them being the injection time of cell therapy after reperfusion. This paper aims to investigate the short-term effects of timing on the efficacy of bone marrow-derived mononuclear cell transplantation after acute myocardial infarction. A systematic literature search of PUBMED, EMBASE, European Society of Cardiology, and American Heart Association databases was made on randomized controlled trials with at least 3-month follow-up data for patients with AMI undergoing percutaneous coronary intervention (PCI) and receiving intracoronary autologous BMSC transfer subsequently. A total of 12 trials with 1061 patients were selected for analysis. Compared to baseline level, BMSC transfer within 24 hours of PCI significantly improved left ventricular ejection fraction (LVEF; 3.44% increase, 95% confidence interval [CI]: 2.20%-4.68%, P< 0.00001). The “3-7 days after PCI” subgroup also showed notable improvements in LVEF (LVEF; 2.52% increase, 95% confidence interval [CI]: 1.01%-4.04%, P = 0.001). However, in the subgroups that received BMSC transplantation either 7-14 days after PCI or later than 15 days after PCI, there was no significant effect on treatment outcome.

Efficacy of Cellular Therapy for Azoospermia in Animal Models: A Systematic Review and Meta-Analysis

This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess the therapeutic effectiveness of stem cell transplant, using different transplant methods, injection sites, and stem cell types, and the reliability of this approach in different animal species. PubMed, the Cochrane Library, and Embase were searched for studies published from January 2006 to February 2022 that evaluated the use of stem cell transplant to treat azoospermia. We included 18 studies and conducted the analyses using Review Manager 5.2 software. Expression of the meiosis-related genes Vasa, Scp3, and Dazl and the average hematoxylin and eosin- positive staining area were improved after stem cell transplant. Subgroup analyses by mode of transplant showed higher expression of Scp3 and Dazl in the xenotransplant group. Although subgroup analyses by injection site showed that the seminiferous tubule group showed the most significant effect on Scp3 expression, spermatogenesis and repair of damaged testis were induced in the tunica albuginea group. The testicular torsion group also induced high levels of Scp3. Another subgroup analysis by stem cell type showed that umbilical cord mesenchymal stem cells promoted the highest expression of meiosis-related genes and successfully induced spermatogenesis and the repair of damaged testis. Urine-derived stem cells, spermatogonial stem cells, and amniotic fluid-derived stem cells showed significantly therapeutic effects; however, more studies are needed for definitive conclusions. Subgroup analyses by type of azoospermia animal model indicated that the use of stem cell transplant in rat or mouse models had an obvious therapeutic effect, but no significant therapeutic effect was seen in azoospermia hamsters. The meta-analysis confirmed that stem cell transplant can effectively treat azoospermia in animal models. Xenotransplant is shown to enhance the therapeutic effects of stem cell transplant on azoospermia.

Stem Cell Transplantation and Cell-Free Treatment for Periodontal Regeneration.

Increasing attention has been paid to cell-based medicines. Many in vivo and in vitro studies have demonstrated the efficacy of stem cell transplantation for the regeneration of periodontal tissues over the past 20 years. Although positive evidence has accumulated regarding periodontal regeneration using stem cells, the exact mechanism of tissue regeneration is still largely unknown. This review outlines the practicality and emerging problems of stem cell transplantation therapy for periodontal regeneration. In addition, possible solutions to these problems and cell-free treatment are discussed.

The Safety and Efficacy of Stem Cell Therapy as an Emerging Therapy for ALS: A Systematic Review of Controlled Clinical Trials

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a heterogeneous course that ultimately leads to death. Currently, there is no cure, and new treatments that can slow the progression of the disease are needed. Stem cell (SC) transplantation is an emerging therapy that has shown a lot of potential in recent clinical trials. This review is aimed to examine the results of various clinical trials on this topic, thus assessing the safety and efficacy of SC transplantation as a potential treatment for ALS. We identified 748 studies in our search, of which 134 full-text studies were assessed for eligibility. Six studies met the inclusion criteria and were included in this review. Although some of the included studies showed the positive effect of SC transplantation, other studies found that there was no significant difference compared to the control group. We observed more positive effects with bone marrow mesenchymal stem cells (BM-MSC) treatments than Granulocyte colony-stimulating factor (G-CSF) ones. However, other factors, such as route of administration, number of doses, and number of cells per dose, could also play a role in this discrepancy. Based on this information, we conclude that more properly conducted clinical trials are needed to appreciate the benefit of this treatment.

Stem Cell Transplantation for Congenital Dyserythropoietic Anemia. a Retrospective Study on Behalf of Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplantation Group (EBMT)

INTRODUCTIONCongenital Dyserythropoietic Anemias (CDA) are a group of heterogeneous bone marrow disorders characterized by anemia, ineffective erythropoiesis and specific cytomorphological features involving bone marrow late erythroblasts. Patients may also show some dysmorphisms involving fingers and nails. In the last few years genetic mutation explaining most cases of CDA have been identified.The management of the disease is generally limited to blood transfusion and iron chelation. Some report have shown the efficacy of stem cell transplantation (SCT) as the only curative option for this disease, however data from literature is scarce and limited to a very small number of casesIn this retrospective study we describe the outcome of Stem Cell Transplantation in patients with CDA reported in the EBMT data base.PATIENTS AND METHODSThe study was conducted on behalf of Severe Aplastic Anemia Working Party (SAAWP) of the EBMT and was based on data of patients affected with CDA who underwent SCT and registered in the EBMT Data Base. Clinical information of the disease and details on transplant procedures and follow-up were collected by a specific form distributed to Centres participating in the study.RESULTSBetween 1996-2016, 39 patients (22 males-17 females) whose median age was 5.1 yo (range 0.9-38.2) underwent SCT from matched sibling donor (20, 51%), unrelated donor (17, 44%) or from other relatives (2, 5%) using bone marrow (30, 77%), peripheral blood (7, 18%) or cord blood (2, 5%) as cell source. All patients but one received a myeloblative regimen. Patients' characteristics and transplants outcome details are shown in Table 1. Median days to neutrophils and platelets engraftment were 21 and 34, respectively. Secondary graft failure occurred in 8 patients (20%). Median follow-up was 44 months (range 13-71). Overall survival at 36 months was 70%. Patients who were transplanted with iron overload and who were transplanted from unrelated donor had a significantly inferior outcome (36 month OS: 51% vs 92%, p =0.05 and 45% vs 90%, p 0.007, respectively).CONCLUSIONTo the best of our knowledge, this is the largest reported cohort of patients transplanted for CDA showing that family donor transplants have a better outcome and that iron overload negatively affects the procedure as reported in other red cell disorders. [Display omitted] DisclosuresPeffault De Latour:Amgen: Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

Economic Burden of Stem Cell Transplant Among Patients with Multiple Myeloma

Introduction: Multiple Myeloma (MM) is a rare hematologic malignancy, accounting for 12% of all hematologic cancers. Conventional treatment includes a combination of induction chemotherapy followed by stem-cell transplantation (SCT) for younger patients without significant renal impairment. While the efficacy of SCT in various clinical settings of MM are frequently explored, real-world data on impact of SCT on healthcare resource use (HRU) and costs among patients with MM are limited. This study compared HRU and costs for MM patients with and without SCT in the US.Methods: This retrospective analysis used the MarketScan administrative claims data to select patients newly diagnosed with MM (ICD-9-CM 203.0x) and at least 18 years of age during 7/1/2006- 9/30/2015 (first MM diagnosis = index date). Continuous health plan enrollment for 12 months prior to (baseline) and >3 months after index date (minimum follow-up) was required. Patients were censored at the earliest of disenrollment, death (inpatient or from the social security administration [SSA] death index), or end of study period (12/31/2015). Per-patient per year (PPPY) all-cause and MM-related HRU and costs were calculated during follow-up and compared between patients with SCT versus [vs.] without SCT. MM-related HRU and medical costs required a MM diagnosis code on the claim (primary discharge diagnosis for hospitalizations, any position on the claim for outpatient services). Costs were adjusted to 2016 USD using the medical component of consumer price index. Propensity scores were used to match patients 1:1 on baseline demographic and comorbid conditions using the nearest neighbor approach to adjust for differences between patients with and without SCT.Results: Of the 14,229 newly diagnosed MM patients selected for analysis, 18.8% (N=2,669) received a SCT, of which 99.9% (N=2,667) were matched to MM patients without a SCT. Matched patients were well balanced on the following criteria: age (mean 56.7 [SD 8.2] and 57.4 [SD 8.5] years); gender (57.4% and 57.5% male); Charlson comorbidity index (mean 1.7 [SD 2.2] and 1.7 [SD 2.1]); baseline individual comorbid conditions (anemia [32.3% and 30.9%], renal impairment [7.0% and 6.5%], bone-related [32.6% and 30.3%], cardiac dysfunction [36.4% and 36.0%]). Total all-cause and MM-related healthcare costs PPPY were $114,242 and $110,116 higher among patients with a SCT (vs. patients without a SCT). Similarly, patients with a SCT (vs. patients without a SCT) incurred $55,663 and $49,803 higher all-cause and MM-related costs for hospitalizations, and $39,852 and $33,883 higher all-cause and MM-related costs for outpatient services. MM treatment costs (drug and administration costs) PPPY were also $26,430 higher among patients with a SCT (vs. patients without a SCT). Higher costs among patients with a SCT were driven by increased HRU for both inpatient and outpatient services across the majority of categories (Table). Among the subset linked to the SSA death index (SCT N= 1,553 and non-SCT N=1,583) the median survival time 907 vs 743 days (p<0.001) among patients with a SCT vs. patients without a SCT and the proportion with a death was 10.4% and 12.8% (p=0.042). The difference in median survival time between groups was less pronounced for patients with an index date in a later year; 2006-2011 vs. 2012-2015 (Table).Conclusions: Results show that among age-, gender-, and comorbidity- matched MM patients, management with SCT is associated with higher all-cause and MM-related HRU and costs and increased survival. An examination of the predictors of management with or without SCT and associated outcomes will inform the relative value of therapeutic strategies for MM patients as well as help optimally triage healthcare resources. [Display omitted] DisclosuresAilawadhi:Pharmacyclics: Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Panjabi:Amgen Inc.: Employment, Equity Ownership. Princic:Truven Health Analytics, IBM Company: Employment. Fowler:Truven Health Analytics, IBM Company: Employment. Tran:Truven Health Analytics, IBM Company: Employment. Gatta:Amgen Inc.: Employment, Equity Ownership. Medhekar:Amgen Inc.: Employment, Equity Ownership.

Stem Cell Transplantation Efficacy in Cerebral Palsy: A Physical Therapist Perspective

Background and Purpose&#x0D; Children with spastic cerebral palsy usually display elevation in muscle tone, a decline in gross motor functional abilities , feeding problems and sometimes it may accompanied by visual problems. Studies on stem cell treatment are in their early stages concerning their effect on cerebral palsy. &#x0D; Methods &#x0D; A child with spastic cerebral palsy on level v on gross motor function classification system was selected for autologous bone marrow derived mononuclear transplantation cell. Muscle tone, gross, fine motor abilities, feeding abilities and visual abilities were assessed on 4 occasions, prior the transplantation, immediately after the transplantation, after 6 months and after 1 year.&#x0D; Results No effect of stem cell transplantation was shown on the child.&#x0D; Conclusion Further research studies should be done on the subject but using different population rather than children on level V Gross motor function classification system

A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review.

Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.

Narrative review of stem cell therapy for ischemic brain injury.

Ischemic brain injury is a common cause of long-term neurological deficits in children as well as adults, and no efficient treatments could reverse the sequelae in clinic till now. Stem cells have the capacity of self-renewal and multilineage differentiation. The therapeutic efficacy of stem cell transplantation for ischemic brain injury have been tested for many years. The grafts could survive and mature in the ischemic brain environment. Stem cell transplantation could improve functional recovery of ischemic brain injury models in pre-clinical trials. The potential mechanisms included cell replacement, release of neurotrophic and anti-inflammatory factors, immunoregulation as well as activation of endogenous neurogenesis. Besides, many clinical trials were conducted and some of trials already had preliminary results. From the current published data, cell transplantation for clinical application is safe and feasible. No severe adverse events and tumorigenesis were reported. While the therapeutic efficacy of stem cell therapy in clinic still needs more evidences. In this review, we overviewed the studies about stem cell therapy for ischemic brain injury. Different types of stem cells used for transplantation as well as the therapeutic mechanisms were discussed in detail. The related pre-clinical and clinical trials were summarized into two separate tables. In addition, we also discussed the unsolved problems and concerns about stem cell therapy for ischemic brain injury that need to be overcome before clinic transformation.

Evaluation of the Clinical Efficacy of Stem Cell Transplantation in the Treatment of Spinal Cord Injury: A Systematic Review and Meta-analysis

Stem cell transplantation has been applied to treat spinal cord injury (SCI) in clinical trials for many years. However, the clinical efficacies of stem cell transplantation in SCI have been quite diverse. The purpose of our study was to systematically investigate the efficacy of stem cell transplantation in patients with SCI. The PubMed, Web of Science, Ovid-Medline, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang, and SinoMed databases were searched until October 27, 2020. Quantitative and qualitative data were analyzed by Review Manager 5.3 and R. Nine studies (n = 328) were included, and the overall risk of bias was moderate. The ASIA Impairment Scale (AIS) grading improvement rate was analyzed in favor of stem cell transplantation group [odds ratio (OR) = 6.06, 95% confidence interval (CI): 3.16–11.62, P < 0.00001]. Urodynamic indices also showed improvement in bladder function. In subgroup analyses, the results indicated that in patients with complete (AIS A) SCI, with the application of cell numbers between n*(107–108), two cell types (i.e., bone marrow–derived mesenchymal stem cells and bone marrow mononuclears), and treatment time of more than 6 months, stem cell transplantation was more beneficial for sensorimotor function (P < 0.05 for all groups). The risk of fever incidence in the stem cell transplantation group was 4.22 (95% CI: 1.7–10.22, P = 0.001), and principal component analysis (PCA) suggested it was more related to transplanted cell numbers. Thus, stem cell transplantation can promote functional recovery in SCI patients. Moreover, the type and quantity of transplanted stem cells and treatment time are important factors affecting the therapeutic effect of stem cell transplantation in SCI. Further studies are needed to evaluate the effects and elucidate the mechanisms of these factors on stem cell therapy in SCI.

COMPARATIVE STUDY OF THE EFFICACY OF STEM CELLS IN CORNEAL REGENERATION IN A CHEMICAL BURN IN RABBITS

Objectives: This study compares the efficacy of stem cell transplantation in corneal regeneration and restoration of the limbic deficit in an experimental chemical burn in rabbits.&#x0D; Methods: Biopsy was performed of the limbus and the chemical burns for all rabbits, and we collected the amniotic membranes from a pregnant female rabbit. We kept a control group without transplantation, to study spontaneous and natural healing, and we transplanted the stem cells produced in vitro under the corneal epithelium burned. To compare the result, we tested a group for amniotic stem cell transplantation, a group for limbal stem cell graft, and another group for combined transplantation of both types of stem cells.&#x0D; Results: Transplanted rabbits develop permanent unilateral blindness due to a severe limbic deficit. The group receiving only amniotic stem cells shows temporary anatomical improvement without functional recovery. The two groups receiving limbal stem cells alone or combined with amniotic stem cells showed anatomical and functional satisfaction with quick recovery time for the combined transplantation.&#x0D; Conclusions: A simple chemical burn can establish permanent blindness. When the limbic deficit is important, spontaneous healing is not available. Transplantation of stem cell transplant is the only way to repair this deficit and regenerate the cornea. Only limbic stem cells can be sufficient. Amniotic stem cells can support and speed up the healing time when it combined to limbal stem cells graft. &#x0D; Peer Review History: &#x0D; Received 23 July 2020; Revised 14 August; Accepted 28 August, Available online 15 September 2020&#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 5.0/10&#x0D; Average Peer review marks at publication stage: 7.5/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Mohamed Amin El-Emam&#x0D; Affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria (PUA), Alexandria, Egypt.&#x0D; E-mail: mohamed.elemam@pua.edu.eg&#x0D; &#x0D; Name: Francesco Ferrara&#x0D; Affiliation: USL Umbria 1, Perugia, Italy&#x0D; E-mail: francesco.ferrara@uslumbria1.it&#x0D; &#x0D; Name: Maged Almezgagi&#x0D; Affiliation: Department of Immunology, Medical College of Qinghai University, Qinghai Xining 810001, China&#x0D; E-mail: 1902244017@qq.com&#x0D; &#x0D; Name: Dr. Asia Selman Abdullah&#x0D; Affiliation: University of Basrah, Iraq&#x0D; E-mail: asiaselman2016@gmail.com&#x0D; &#x0D; Comments of reviewer(s): &#x0D;

IBCL-176: Single-Centre Experience with Stem-Cell Transplantation in Patients with Transformed Lymphoma: A Potential Curative Option

Context: Outcomes of patients with transformed lymphoma have historically been poor, prompting many centres to include stem-cell transplant (SCT) as part of the treatment strategy. However, several studies in the rituximab era suggest that survival may be more favourable than previously recognized, questioning the need for such intensive therapies. Objective: We analyzed the efficacy of SCT in transformed lymphomas at a single reference Transplant Unit. Design: We collected data from 51 patients; the indication was a diagnosis of diffuse large B-cell lymphoma (DLBCL) transformed from an indolent lymphoma, from 1995 to 2018. Of them, 36 received an auto-SCT and 15 an allo-SCT. Results: Median age was 60 (range, 40-69) and 52 (range, 35-65) years for patients receiving auto-SCT and allo-SCT, respectively. Patients in the allo-SCT group had been more intensively pretreated, as 13 (87%) patients received >3 lines of treatment before SCT and 13 (87%) underwent a previous auto-SCT, whereas patients in the auto-SCT group were pretreated with a median of 2 (range, 1 to 4) lines of treatment. Regarding disease status at transplant, most patients (78% and 73% in the auto and allo-SCT groups, respectively) were transplanted in complete remission (CR). All auto-SCT patients received BEAM as conditioning regimen, whereas patients in the allo-SCT group received several fludarabine-based combinations. Transplant-related mortality (TRM) was 3.2% and 27% in the auto and allo-SCT groups, respectively. With a median follow-up of 61 and 50 months,4-year overall survival (OS) and progression-free-survival (PFS) were 87% and 76%, for the auto-SCT patients, and 52% and 56%, respectively, for the allo-SCT patients. In the auto-SCT group, 12 (33%) patients experienced disease progression and 7 (19.5%) died (5 [13.9%] from lymphoma), whereas in the allo-SCT group, only 2 (13%) patients had disease progression but 4 (27%) died due to transplant-related causes. Conclusions: SCT is a potentially curative option for patients with transformed lymphoma, since more than a half of patients are long-term survivors. Progression is the major cause of failure in auto-SCT whereas allo-SCT patients died because of toxicity. Efforts need to be made to identify patients who do not benefit from auto-SCT to avoid toxicity.

Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair

BackgroundAge and other cardiovascular risk factors have been reported to impair the activities of mesenchymal stem cells (MSCs), which will affect the efficacy of stem cell transplantation. The objective of the study is to investigate whether exosomes derived from human umbilical cord MSCs (UMSCs) could enhance the activities of bone marrow MSCs from old person (OMSCs), and improve their capacity for cardiac repair.MethodsExosomes extracted from conditioned medium of UMSCs were used to treat OMSCs to generate OMSCsExo. The key molecule in the exosomes that have potential to rejuvenate aged MSCs were screened, and the role of OMSC was tested in the mouse model of mycardial infarction (MI).ResultsWe found the activity of senescence-associated β-galactosidase and the expression of aging-related factors such as p53, p21, and p16 were significantly higher in OMSCs than those in UMSCs. After treatment with UMSC exosomes, these senescence phenotypes of OMSCs were remarkably reduced. The proliferation, migration, differentiation, and anti-apoptotic and paracrine effect were increased in OMSCsExo. In vivo study, mice with cardiac infarction had significantly better cardiac function, less fibrosis, and more angiogenesis after they were injected with OMSCsExo as compared with those with OMSC. There was more miR-136 expression in UMSCs and OMSCsExo than in OMSCs. Upregulation of miR-136 by transfection of miR-136 mimic into OMSCs significantly attenuated the apoptosis and senescence of OMSCs. Apoptotic peptidase activating factor (Apaf1) was found to be the downstream gene that is negatively regulated by miR-136 via directly targeting at its 3′UTR.ConclusionOur data suggest that exosomes from young MSCs can improve activities of aged MSCs and enhance their function for myocardial repair by transferring exosomal miR-136 and downregulating Apaf1.

Traumatic Brain Injury and Stem Cells: An Overview of Clinical Trials, the Current Treatments and Future Therapeutic Approaches.

Traumatic brain injury represents physical damage to the brain tissue that induces transitory or permanent neurological disabilities. The traumatic injury activates an important inflammatory response, followed by a cascade of events that lead to neuronal loss and further brain damage. Maintaining proper ventilation, a normal level of oxygenation, and adequate blood pressure are the main therapeutic strategies performed after injury. Surgery is often necessary for patients with more serious injuries. However, to date, there are no therapies that completely resolve the brain damage suffered following the trauma. Stem cells, due to their capacity to differentiate into neuronal cells and through releasing neurotrophic factors, seem to be a valid strategy to use in the treatment of traumatic brain injury. The purpose of this review is to provide an overview of clinical trials, aimed to evaluate the use of stem cell-based therapy in traumatic brain injury. These studies aim to assess the safety and efficacy of stem cells in this disease. The results available so far are few; therefore, future studies need in order to evaluate the safety and efficacy of stem cell transplantation in traumatic brain injury.

Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials.

Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005–2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.

Cell-Based Therapy for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease characterized by the degeneration of lower motor neurons in the spinal cord, leading to progressive paralysis and early death in the severe cases. SMA is primarily caused bythe mutations in the gene of SMN (survival motor neuron).Moreresearch has focused on the development of SMN-targeted replacement therapy for SMA. The first US Food and Drug Administration (FDA)-approved modified antisense oligonucleotide (nusinersen) to treat SMA is to reverse intronic splicing silencer of SMN to produce fully functional SMN2. Recently, stem cell transplantation hasshown the potential to repair the injured tissue and differentiate into neurons to rescue the phenotypes of SMA in animal models. In this chapter, we first review the clinical, genetic, and pathogenic mechanisms of SMA. Then, we discuss current pharmacological treatments and point out the therapeutic efficacy of stem cell transplantation and future directions and priorities for SMA.