Hematopoietic Stem Cell Therapy Research Articles

Crohn’s Disease: Hematopoietic and Mesenchymal Stem Cell Therapy as Potential Treatment

Purpose: The purpose of this work was to comprehensively review literature to determine the safety and efficacy of stem cells for the treatment of Crohn’s disease and compare the effects of hematopoietic stem cells (HSCs) to that of mesenchymal stem cells (MSCs). Results: The data search included 5 animal models and clinical trials found on PubMed. The 5 studies included for HSCs and the 15 trails for MSCs found them to be a safe and effective as a treatment option (allogeneic and autologous bone marrow and adipose derived) for CD except for one multicenter randomized trial for HSC therapy. Most trials investigate the impact of stem cells specifically on perianal fistula, a common occurrence in patients with CD. Conclusion: While both HSCs and MSCs proved their safety and efficacy, MSC studies showed a greater therapeutic effect over HSCs. Adipose MSCs and Bone Marrow Derived MSCs reached similar clinical healing rates, with studies backing support for both sides. Across the board, autologous stem cell transplants proved to be safer and more effective compared to their allogeneic counterparts.

Hematopoietic Stem Cell Derived Functional Osteoblasts Exhibit Therapeutic Efficacy in a Murine Model of <i>Osteogenesis Imperfecta</i>

Currently, there is no cure for Osteogenesis imperfecta (OI) - a debilitating pediatric skeletal dysplasia. Herein we show that hematopoietic stem cell (HSC) therapy holds promise in treating OI. Using single cell HSC transplantation in lethally irradiated oim/oim mice, we demonstrate significant improvements in bone morphometric, mechanics and turnover parameters. Importantly, we highlight that HSCs cause these improvements due to their unique property of differentiating into osteoblasts/osteocytes, depositing healthy collagen- an attribute thus far assigned only to mesenchymal stem cells. To confirm this HSC plasticity, lineage tracing was done by transplanting oim/oim with HSCs from two specific transgenic mice - VavR, in which all hematopoietic cells are GFP + and pOBCol2.3GFP, where GFP is expressed only in osteoblasts/osteocytes. In both models, transplanted oim/oim mice demonstrated presence of GFP + HSC-derived osteoblasts/osteocytes in bones. These studies unequivocally establish that HSCs differentiate into osteoblasts/osteocytes and HSC transplantation can provide a new translational approach for OI.

Autologous Hematopoietic Stem Cell Therapy of the Subjects with Systemic Sclerosis: Electromyographic Results of the Masticatory Muscles.

Musculoskeletal system impairment is a major cause of functional alterations in subjects with systemic sclerosis. Autologous hematopoietic stem cell therapy (AHSCT) may have an important role in the treatment functional of systemic sclerosis patients. The aim of this pilot study was to assess whether AHSCT interferes with the electromyographic activity of the masseter and temporalis muscles of subjects with systemic sclerosis. Before transplantation, seven subjects with systemic sclerosis (mean age [± SD], 40.1 ± 9.6 years) underwent electromyographic analysis of the masseter and temporalis muscles in mandibular tasks at rest, right and left laterality, protrusion and maximum voluntary contraction. Two months after AHSCT, the subjects re-evaluated using the same methods. Data were analyzed using the repeated-measure test, with p<0.05 considered to be statistically significant. Two months after AHSCT, there was reduction in normalized electromyographic activity in the dental clenching in maximal voluntary contraction, with significant differences, for the left temporal muscle (p=0.04). AHSCT in subjects with systemic sclerosis promotes alterations in stomatognathic system function, especially those related to electromyographic activity of masticatory muscles.

Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Purpose of reviewIn this review, we summarize the recently published literature that demonstrates the efficacy and safety of autologous haematopoietic stem cell therapy (AHSCT) in multiple sclerosis (MS) and highlight the importance of supportive care required for the safe and well-tolerated delivery of AHSCT.Recent findingsMS is an autoimmune inflammatory and degenerative disorder of the central nervous system (CNS). In the majority of patients, the illness runs a relapsing remitting course (RRMS), culminating in a secondary progressive phase with gradual accumulation of fixed disabilities. Currently available disease-modifying therapies suppress CNS inflammation but have a limited effect on preventing disease progression for which there remains no effective therapy. Over the last two decades, there has been increasing evidence that AHSCT is a highly effective therapeutic strategy for treatment-resistant inflammatory types of MS, especially RRMS. Concerns about the safety of AHSCT in MS, usually a nonlife-threatening disease, have previously limited its use. However, AHSCT can now be delivered safely with major long-term benefits because of increasing transplant centre experience, judicious patient selection and good supportive care.SummaryMS is currently the fastest growing indication for AHSCT in Europe. Supportive care before, during and after the transplant period is key to the successful delivery of AHSCT.

Saving whom? The ethical challenges of harvesting tissue from savior siblings.

To discuss the ethical challenges for the therapeutic team when dealing with a young savior sibling as a potential tissue donor. Savior siblings are children that are created to serve a sibling as a donor of umbilical cord blood, bone marrow, or peripheral blood from which hematopoietic stem cells are derived. These cells are used for hematopoietic stem cell therapy, which is the only curative treatment for certain hemoglobinopathies. We used a case including a 19-year-old thalassemia patient and his two and a half year old sister from our practice as ethics consultants. Our methodological basis is the principlism approach by Beauchamp and Childress, consisting of four principles: autonomy, non-maleficence, beneficence, and justice. We found that the main conflict arises between the autonomy of the savior sibling as well as the non-maleficence regarding her and the beneficence of the thalassemia patient. Decision-making is complex when decisions within the family are concerned, especially when non-competent young children are involved. The therapeutic team does not only have to recognize the principal vulnerability of children but also the different scales of vulnerability depending on their age.

A Novel Pathological ARSB Mutation (c.870G>A; p.Trp290stop) in Mucopolysaccharidosis Type VI Patients

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder, characterized by the deficiency of the arylsulfatase B enzyme. The clinical phenotype and severity of the illness varies according to the residual enzyme activity. Typical features are a short stature, shortened trunk, protuberant abdomen, flexed-knee stance, arched back, corneal clouding, joint stiffness and contractures as well as a waddling gait. Patients typically have Hurler-like dysmorphic facial features: microcephaly, prominent forehead and eyes, a broad nose, low nasal bridge, thick lips, and hyperplastic gums with widely spaced teeth. Complications of the illness include obstructive airway, cardiac valvular problems, splenomegaly, hernias, and pneumonia. Unlike other MPS diseases, MPS VI is characterized by normal intellectual development. Since the disease is due to deficient glycosaminoglycan (mucopolysaccharide) metabolism, elevated urinary glycosaminoglycan levels are a main indicator of MPS. Diagnosis is confirmed by enzyme assays, specifically low arylsulfatase B activity in conjunction with the normal activity of other lysosomal enzymes. Enzyme replacement therapy and hematopoietic stem cell therapy are showing positive results in the management of the condition. The more severely affected patients, with a rapidly advancing form of the disease, have a short life span and succumb, most commonly to heart failure, by early adulthood. The frequency of ARSB variants in patients with MPS VI are as follows: 59.5% missense, 13.5% small deletions, 12% nonsense, 5% splice site or intronic variants, 3% small duplications, 3% large deletions, and 1% stop-loss. We report an Albanian family with siblings diagnosed with MPS Vl after clinical examination, biochemical tests, and molecular analysis. Hereby, a novel c.870G>A nonsense homozygous mutation was found responsible for the loss of the enzyme activity.

Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network.

Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies. To this purpose, we conducted a 30-year retro-prospective multicenter study within the Italian Primary Immunodeficiency Network. One hundred eleven patients, diagnosed as typical or atypical SCID according to the European Society for Immune Deficiencies criteria, were included. Patients were subsequently classified based on the genetic alteration, pathogenic mechanism and immunological classification. A positive relationship between the age at onset and the DD was found. SCID patients with later onset were identified only in the last decade of observation. Syndromic SCIDs represented 28% of the cohort. Eight percent of the subjects were diagnosed in Intensive Care Units. Fifty-three percent had an atypical phenotype and most of them exhibited a discordant genotype-immunophenotype. Pre-treatment mortality was higher in atypical and syndromic patients. Our study broadens the knowledge of clinical and laboratory manifestations and genotype/phenotype correlation in patients with SCID and may facilitate the diagnosis of both typical and atypical forms of the disease in countries where newborn screening programs have not yet been implemented.

Effects of Hematopoietic Stem Cells on Liver Cirrhosis of Albino Rats

AbstractBackground: Liver cirrhosis is a common serious disease in Egypt due to high incidence rate of infectious liver diseases; hepatitis. Application of Hematopoietic Stem Cells (HSCs) may provide a hope for patients with liver cirrhosis as it is not only safe but also to avoid hazardous complications and immunosuppressive drug following liver transplantation.Aim of Study: Evaluation of the effects of CD34+ hemat-opoietic stem cells in regeneration of hepatic tissue as a new therapy for cirrhotic liver.Material and Methods: Forty five male albino rats were divided into four groups: Control group: Include 18 rats injected with olive oil subcutaneously, (carbon tetrachloride treated group): 9 rats received carbon tetrachloride subcuta-neously, (carbon tetrachloride/hematopiotic stem cells treated group): 9 rats injected with hematopiotic stem cells after induction of liver cirrhosis by carbon tetrachloride and (carbon tetrachloride/fibroblast treated group): 9 rats injected with fibroblast cells after carbon tetrachloride induced liver cirrho-sis. For histological and biochemical study of liver and blood samples were taken from all rats.Results: Rats of carbon tetrachloride treated group & carbon tetrachloride/fibroblast treated group indicated significant changes in liver histological structures accompanied with significant decline of liver function tests. Injection of HSC showed marked improvement in both histological picture and biochemical profile.Conclusion: This study indicates the effectiveness of human CD34+ hematopoietic stem cells in amelioration of CCl4 induced liver cirrhosis in rats. So, treatment with he-matopoietic stem cells therapy can be considered a new hope for cirrhotic patients, especially in Egypt.

Bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplantation and maintenance in 200 patients with multiple myeloma: long-term follow-up results from single center

目的评价含硼替佐米方案诱导-自体造血干细胞移植（ASCT）-维持治疗的整体策略治疗多发性骨髓瘤（MM）的疗效和安全性。方法回顾性和前瞻性分析2006年12月1日至2018年4月30日接受含硼替佐米方案诱导-ASCT-维持治疗的整体策略的200例MM患者，分析不同阶段的近期疗效以及长生存，动态分析不同阶段影响疾病进展时间（TTP）和总生存（OS）的危险因素，总结移植后TTP≥6年患者的临床特征。结果诱导、移植和维持治疗后的完全缓解（CR）率和≥非常好的部分缓解（VGPR）率分别为31.0%和75.5%、51.8%和87.7%、73.6%和93.4%，诱导4个疗程和≥5个疗程疗效差异无统计学意义。流式细胞术检测微小残留病（MRD）阴性率在诱导后、移植后3个月分别为17.6%和38.2%，随着维持治疗的进行，MRD转阴率逐渐增加。大剂量环磷酰胺+G-CSF动员成功率为95.5%，移植相关死亡率为0。该组患者中位TTP 75.3个月，中位OS 99.5个月，诱导后达CR和MRD阴性患者TTP明显延长，三药诱导和早期移植患者的TTP和OS均明显延长。初诊时LDH≥240 U/L、高危FISH、ISS分期和HBsAg是影响TTP的危险因素，移植后和维持后只有MRD和高危FISH是影响患者TTP的危险因素。移植后TTP≥6年患者具有以下临床特点：M蛋白类型为轻链型，ISS分期为Ⅰ期，起病时HGB和PLT正常、LDH不高，HBsAg阴性，无17p−，对治疗反应好且能维持。结论含硼替佐米诱导-ASCT-维持治疗的整体治疗策略可以明显提高MM患者近期疗效和长生存，不同阶段影响TTP的预后因素是动态变化的，对治疗的反应尤其MRD水平的缓解在预后因素中扮演了更重要的角色。

Non-thermal atmospheric pressure plasma is an excellent tool to activate proliferation in various mesoderm-derived human adult stem cells

Adult stem cells are capable of self-renewal and differentiation into specific cell types in tissues and have high potential for stem cell therapy. Mesenchymal and hematopoietic stem cells are easily attainable from the human body and have become applicable tools for adult stem cell therapy. However, there are still technical barriers for the application of mesenchymal and hematopoietic stem cells for therapy, such as the small number of cell populations, high risk of contamination, and loss of their stemness properties in vitro. In our previous study, we showed that non-thermal atmospheric pressure plasma (NTAPP) promoted the proliferation of adipose tissue-derived stem cells (ASCs) by 1.6-fold on average, while maintaining their stemness. Here, we examined the feasibility of NTAPP as a tool to activate the proliferation of mesenchymal and hematopoietic stem cells in vitro without affecting their stem cell characteristics. NTAPP increased the proliferation of bone marrow-derived stem cells (BM-MSCs) and hematopoietic stem cells (HSCs) by 1.8- and 2-fold, respectively, when compared to that of untreated cells. As observed in ASCs, NTAPP exposure also activated the expression of stem cell-specific surface markers, CD44 and CD105, by 5-fold in BM-MSCs, when compared to that in unexposed control cells in a low glucose medium with a low concentration of basic fibroblast growth factor (b-FGF). In addition, NTAPP exposure highly augmented the mRNA expression of well-known pluripotent genes for stemness, such as Oct4, Sox2, and Nanog in ASCs and BM-MSCs when compared to that in unexposed control cells. When cell cycle progression was examined, the G1-S shift was accelerated, and expression of PCNA was increased in NTAPP-exposed ASCs when compared to that in untreated control cells, suggesting that NTAPP activated G1-S transition. Taken together, these results demonstrated that NTAPP activated the proliferation of various mesodermal-derived human adult stem cells by accelerating the G1-S transition while maintaining their pluripotency and stemness, strongly suggesting that NTAPP can be an efficient tool for expanding the population of various adult stem cells in vitro for medical applications.

Tuberculosis: A Complication after Hematopoietic Stem Cell Therapy (HSCT) and Bone Marrow Transplant

Tuberculosis: A Complication after Hematopoietic Stem Cell Therapy (HSCT) and Bone Marrow Transplant

An Engineered Cell-Traceable Model of Reticular Dysgenesis in Human Hematopoietic Stem Cells Linking Metabolism and Differentiation

Hematopoietic stem cell (HSC) differentiation is accompanied by a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) to meet the increasing energy demand during proliferation and differentiation. However, the role of mitochondrial metabolism in HSC differentiation goes beyond ATP production. Metabolites generated during mitochondrial metabolism may impact in HSC fate decisions through stable epigenetic modifications. Despite some progress in understanding mitochondrial communication during HSC development, their role in human hematopoiesis remains largely elusive, where the lack of appropriate model systems poses a major obstacle. Reticular Dysgenesis (RD), a rare and particularly severe form of severe combined immunodeficiency (SCID), offers an attractive model for studying the role of mitochondrial metabolism in hematopoiesis. RD is an autosomal recessive disease caused by biallelic mutations of the mitochondrial enzyme Adenylate Kinase 2 (AK2). AK2 catalyzes the reversible phosphorylation of adenosine monophosphate (AMP) to adenosine diphosphate (ADP), which serves as the substrate for the ATP synthase. In addition to defective lymphocyte development typical of classic SCID, RD patients also suffer from impaired myeloid development, suggestive of a global defect in hematopoiesis. In a human induced pluripotent stem cell (iPSC) model for RD, hematopoietic stem and progenitor cells (HSPCs) recapitulate a profound maturation arrest of the myeloid lineage, increased oxidative stress and an energy-depleted metabolite and transcriptional profile. We hypothesize that AK2 defects drive hematopoietic cell fate decisions through changes in metabolites that regulate the activities of DNA/histone modifying enzymes and result in stable epigenetic modifications.Methods: Since iPSCs are not suitable to model the epigenetic characteristics of definitive hematopoiesis, we developed a novel model system in which we deleted AK2 in primary human HSCs using CRISPR/Cas9 gene editing technique. We found a highly effective single-guide RNA (sgRNA) targeting the catalytic LID domain of the AK2 gene to introduce directed DNA double stranded breaks (DSBs), and use a homologous recombination (HR)-mediated dual reporter system to track and isolate cells with biallelic AK2 disruption.Results: Our single-color GFP reporter system consistently produces a >60% GFP+ population of AK2-targeted CD34+ umbilical cord blood (UCB) cells. With dual GFP/BFP reporters, we were able to achieve 6% GFP/BFP double positive cells with confirmed biallelic AK2 knock-out. Since HR events on one allele are biologically linked to CRISPR/Cas9 mediated DSBs on the other, we assessed insertion and/or deletion (INDEL) frequency and protein expression in a single reporter (GFP+) population of AK2-targeted UCBs. We detected an INDEL frequency of over 90% on the non-HR alleles along with nearly absent AK2 protein expression by Western Blot. These results indicated that the highly efficient single-color reporter system with >60% targeting efficiency is sufficient to achieve an AK2 biallelic knock-out population in primary HSCs. in vitro myeloid differentiation of these AK2-targeted HSCs recapitulates the RD phenotype with impaired neutrophil but preserved monocyte development.Conclusion: This novel disease model for RD will now allow us to examine the cellular and molecular impact of perturbations in metabolism on human HSC development. We will investigate the effect on differentiation potential, metabolite profile, transcriptome and epigenome in vitro as well as in a xenograft mouse model. Elucidating how metabolism governs differentiation and self-renewal of human HSCs will not only advance our basic understanding of many blood and immune diseases, but has important translational implications for improving the use of HSCs in hematopoietic stem cell transplantation, gene and cell therapy. DisclosuresPorteus:CRISPR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Lentiviral vectors in hematopoietic stem cell therapies: mainstay technology, or simply a bridge to gene editing?

Lentiviral vectors in hematopoietic stem cell therapies: mainstay technology, or simply a bridge to gene editing?

An X-Linked Hyper-IgM Patient Followed Successfully for 23 Years without Hematopoietic Stem Cell Transplantation

When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.

Eleven percent intact PGM3 in a severely immunodeficient patient with a novel splice-site mutation, a case report

BackgroundA novel immunodeficiency, frequently accompanied by high serum-IgE, and caused by mutations in the PGM3 gene was described in 2014. To date there are no unique phenotype characteristics for PGM3 deficiency. PGM3 encodes a carbohydrate-modifying enzyme, phosphoglucomutase 3. Null-mutations are quite likely lethal, and to date only missense mutations or small deletions have been reported. Such mutations frequently cause a combination of reduced enzyme activity and protein instability, complicating determination of the enzyme level needed for survival. Here we present the first patient with a homozygous splice-modifying mutation in the PGM3 gene. An A > G substitution at position c.871 + 3 (transcript NM_001199917) is causing a deletion of exon 7 in the majority of PGM3 transcripts. In addition, this case further increases the clinical phenotypes of immunodeficiency caused by PGM3 mutations.Case presentationWe describe the symptoms of a 3-year-old girl who was severely growth retarded, had vascular malformations, extensive eczema, multiple food-allergies, and was prone to infections. Unlike the majority of reported PGM3 deficient patients she lacked skeletal dysplasia and had normal neurocognitive development. In addition to the high serum-IgE, she displayed altered T cell numbers with reduced naïve CD4+ and CD8+ T-cells, increased number of activated effector memory CD8+ T cells and aberrant T-cell functions.The patient was homozygous for a new hypomorphic, splice-modifying mutation in the PGM3 gene, causing severely reduced mRNA levels. In the patient’s cells, we observed 5% intact mRNA and approximately 11% of the protein levels seen in healthy controls.Treatment with allogeneic hematopoietic stem cell therapy was planned, but unfortunately the clinical condition deteriorated with multi-organ failure, which led to her death at 3 years of age.ConclusionsThere is still no specific phenotype identified that distinguishes immunodeficiency caused by PGM3 mutations from other forms of immunodeficiency. The patient described here yields new information on the phenotypic variability among these patients. In addition, since all the synthesized protein is wild-type, it is possible for the first time to estimate the enzyme activity in vivo. The results suggest that1/10 of the normal PGM3 level is sufficient for survival but that it is insufficient for accurate carbohydrate processing.

Critical assessment of the efficiency of CD34 and CD133 antibodies for enrichment of rabbit hematopoietic stem cells.

Rabbits have many hereditary diseases common to humans and are therefore a valuable model for regenerative disease and hematopoietic stem cell (HSC) therapies. Currently, there is no substantial data on the isolation and/or enrichment of rabbit HSCs. This study was initiated to evaluate the efficiency of the commercially available anti-CD34 and anti-CD133 antibodies for the detection and potential enrichment of rabbit HSCs from peripheral blood. PBMCs from rabbit and human blood were labelled with different clones of anti-human CD34 monoclonal antibodies (AC136, 581, and 8G12) and rabbit polyclonal CD34 antibody (pCD34) and anti-human CD133 monoclonal antibodies (AC133 and 293C3). Flow cytometry showed a higher percentage of rabbit CD34+ cells labelled by AC136 in comparison to the clone 581 and pCD34 (P < 0.01). A higher percentage of rabbit CD133+ cells were also detected by 293C3 compared to the AC133 clone (P < 0.01). Therefore, AC136 clone was used for the indirect immunomagnetic enrichment of rabbit CD34+ cells using magnetic-activated cell sorting (MACS). The enrichment of the rabbit CD34+ cells after sorting was low in comparison to human samples (2.4% vs. 39.6%). PCR analyses confirmed the efficient enrichment of human CD34+ cells and the low expression of CD34 mRNA in rabbit positive fraction. In conclusion, the tested antibodies might be suitable for detection, but not for sorting the rabbit CD34+ HSCs and new specific anti-rabbit CD34 antibodies are needed for efficient enrichment of rabbit HSCs. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1278-1289, 2018.

Urticarial vasculitis and subcutaneous nodules in the extremities seen in a patient with mucopolysaccharidosis II after hematopoietic stem cell therapy

Urticarial vasculitis and subcutaneous nodules in the extremities seen in a patient with mucopolysaccharidosis <scp>II</scp> after hematopoietic stem cell therapy

No Evidence of Disease Activity after Five Years of Autologous Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Detailed Report of Five Patients

No Evidence of Disease Activity after Five Years of Autologous Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Detailed Report of Five Patients

Shaping the future of liver surgery: Implementation of experimental insights into liver regeneration.

SummaryBackgroundWhile liver surgery has become a safe and feasible operation technique, the incidence of postoperative liver dysfunction still remains a central problem. Approximately 10% of patients undergoing liver resection were shown to develop liver dysfunction, which is associated with an increased risk of morbidity and mortality. Yet, to date there is no effective treatment option for postoperative liver dysfunction available. The development of postoperative liver dysfunction was linked to a disruption in the liver’s potential to regenerate. Thus, it is importance to elucidate the underlying mechanisms of liver regeneration and to find potential therapeutic targets for the treatment of patients with postoperative liver dysfunction.MethodsA review of the literature was carried out.ResultsWe report on potential future interventions for improvement of liver regeneration after surgical resection. Moreover, we evaluate the benefits and drawbacks of hepatic progenitor cell therapy and hematopoietic stem cell therapy. However, the most significant improvement seems to come from molecular targets. Indeed, von Willebrand factor and its pharmacologic manipulation are among the most promising therapeutic targets to date. Furthermore, using the example of platelet-based therapy, we stress the potentially adverse effects of treatments for postoperative liver dysfunction.ConclusionThe present review reports on the newest advances in the field of regenerative science, but also underlines the need for more research in the field of postoperative liver regeneration, especially in regard to translational studies.

Hematopoietic stem cells from induced pluripotent stem cells - considering the role of microRNA as a cell differentiation regulator.

Although hematopoietic stem cell (HSC) therapy for hematological diseases can lead to a good outcome from the clinical point of view, the limited number of ideal donors, the comorbidity of patients and the increasing number of elderly patients may limit the application of this therapy. HSCs can be generated from induced pluripotent stem cells (iPSCs), which requires the understanding of the bone marrow and liver niches components and function in vivo iPSCs have been extensively applied in several studies involving disease models, drug screening and cellular replacement therapies. However, the somatic reprogramming by transcription factors is a low-efficiency process. Moreover, the reprogramming process is also regulated by microRNAs (miRNAs), which modulate the expression of the transcription factors OCT-4 (also known as POU5F1), SOX-2, KLF-4 and MYC, leading somatic cells to a pluripotent state. In this Review, we present an overview of the challenges of cell reprogramming protocols with regard to HSC generation from iPSCs, and highlight the potential role of miRNAs in cell reprogramming and in the differentiation of induced pluripotent stem cells.