Stem Cells For Treatment Research Articles

Bone marrow mesenchymal stem cells for treatment of pancreatic diseases: Research status and prospects

Bone marrow mesenchymal stem cells for treatment of pancreatic diseases: Research status and prospects

English

English

Autologous Stem Cell Application in Periodontal Regeneration Technique (SAI-PRT) Using PDLSCs Directly From an Extracted Tooth···An Insight.

Periodontal regeneration represents the ultimate goal of periodontal therapy. The current regenerative techniques have limited success rates especially in advanced periodontal defects. Currently the research is focused on novel cell-based approaches for periodontal regeneration to overcome the limitations of existing treatment. The human clinical trial on stem cells based periodontal regeneration is promising. The plethora of animal studies provide sound evidence to support the belief that periodontal ligament stem cells (PDLSCs) can be used for periodontal regeneration. The direct application of autologous periodontal stem cells in treatment of intrabony defects is attempted for the first time in periodontal literature. Stem cell Application in Periodontal Regeneration Technique (SAI-PRT) using direct PDLSCs has overcome the limitations and concerns of ex- vivo stem cell culture methods like high cost, technique sensitivity, loss of stemness during cell passage, genetic manipulation and tumorigenic potential. Clinical feasibility, success and cost effectiveness over currently available techniques are encouraging. The clinical utility of this novel idea is recommended.

Skeletal stem cells and their contribution to skeletal fragility: senescence and rejuvenation.

Age-related osteoporotic fractures are major health care problem worldwide and are the result of impaired bone formation, decreased bone mass and bone fragility. Bone formation is accomplished by skeletal stem cells (SSC) that are recruited to bone surfaces from bone marrow microenvironment. This review discusses targeting SSC to enhance bone formation and to abolish age-related bone fragility in the context of using stem cells for treatment of age-related disorders. Recent studies are presented that have demonstrated that SSC exhibit impaired functions during aging due to intrinsic senescence-related changes as well as the presence of senescent microenvironment. Also, a number of approaches aiming at increasing bone formation through targeting SSC and that include systemic SSC transplantation, systemic SSC targeting using aptamers or antibodies, use of therapeutic screteome and tissue engineering approaches will be presented and discussed.

Propose a Regulatory Framework for Stem Cell Research based on Ethical Guideline

Background : Stem cell research has emerged as one of the most promising research areas in modern biomedicine. However, despite much promise the use and derivation of these cells in many countries is ethically challenging. Stem cell laws are the law, rules, and policy governance concerning the sources, research, and use of stem cells in treatment of human diseases. These laws have been the source of much controversy and vary significantly by country. Methods: Google search was used to find information on the Web about stem cell research in world countries and Iran. Discussion: An ethical guideline in Iran has been recently approved. In compiling this guideline the accumulated experience of the governments and Islamic laws and Persian culture and special look to human health as well as the moral status of the human embryo has been used. Some part of this guideline is licensed research can only take place on embryos created in vitro : embryos that have developed from eggs fertilized outside the body. Most embryos used in stem cell research are embryos that initially created in order to use in fertility treatment, but not used. These 'surplus' IVF embryos, if donated with the full consent of the parents, can be used for research. Conclusion: We propose a regulatory framework based on this moral guideline one of our suggestion for regulation of stem cell research is legal medicine organization.

Implantation of autologous muscle-derived stem cells in treatment of fecal incontinence: results of an experimental pilot study.

BackgroundThe aim of this study is to present results of the implantation of autologous myoblasts into the external anal sphincter (EAS) in ten patients with fecal incontinence.MethodsAfter anatomical and functional assessment of the patients’ EAS, a vastus lateralis muscle open biopsy was performed. Stem cells were extracted from the biopsy specimens and cultured in vitro. Cell suspensions were then administered to the EAS. Patients were scheduled for follow-up visits in 6-week intervals. Total follow-up was 12 months.ResultsAll biopsy and cell implantation procedures were performed without complications. Nine of the patients completed a full 12-month follow-up. There was subjective improvement in six patients (66.7 %). In manometric examinations 18 weeks after implantation, squeeze anal pressures and high-pressure zone length increased in all patients, with particularly significant sphincter function recovery in five patients (55.6 %). Electromyographic (EMG) examination showed an increase in signal amplitude in all patients, detecting elevated numbers of propagating action potentials. Twelve months after implantation two patients experienced deterioration of continence, which was also reflected in the deterioration of manometric and EMG parameters. The remaining four patients (44.4 %) still described their continence as better than before implantation and retained satisfactory functional examination parameters.ConclusionsImplantation of autologous myoblasts gives good short-term results not only in a subjective assessment, but also in objective functional tests. It seems that this promising technology can improve the quality of life of patients with fecal incontinence, but further study is required to achieve better and more persistent results.

Human Embryonic Stem Cells in Treatment of Spinal Cord Injury: A Prospective Study

Background: Spinal cord injury (SCI) is a devastating disease which impacts the patient physically, psychologically and financially. Although the pharmacological and non-pharmacological methods are used, none of them are able to improve the quality of life permanently. Recent advancement in the regenerative medicines has risen a new dawn for treatment of SCI. Method: In the current study, human embryonic stem cells (hESCs) were used on pre-diagnosed chronic SCI patients with informed written and video consent. The cell lines were cultured and maintained in a good manufacturing practice (GMP), good laboratory practice (GLP), and good tissue practice (GTP) compliance laboratory which were free of animal product and chromosomally stable. The patients were scored according to the American Spinal Injury Association (ASIA) scale. There were four treatment phases (T1, T2, T3 and T4) with gap phases. Patient received 0.25 mL of hESCs through intramuscular (IM) route twice daily, 1 mL of hESCs every 10 days through intravenous (IV) route and 1 - 5 mL of hESCs for 5 - 7 days through supplemental routes. Magnetic resonance imaging (MRI) tractography was performed for all the patients before and after the therapy. Result: Of 11 patients at the beginning of therapy, seven patients were on ASIA score A, one patient was on ASIA score B, two patients were on ASIA score C and one patient was on ASIA score D. At the end of treatment, three patients moved to lower scale, i.e. ASIA score D, two patients to ASIA score C and rest all the patients were on ASIA score A. There was a remarkable improvement in the signs and symptoms of patients clinically. No adverse event and teratoma formation was observed. Conclusion: hESC therapy showed remarkable improvement in the clinical symptoms in SCI patients. J Neurol Res. 2015;5(3):213-220 doi: http://dx.doi.org/10.14740/jnr339w

Comparative study between the effect of stem cells and Metacam® on induced arthritis in dogs

Objective of this project was to study the effect of stem cellson the induced arthritis in the dogs as compared with treatment Metacam®. Incomplete fruend'sadjuvant was used to induce arthritis. Twenty five dogsaged 12 month were divided into five groups: 1stgroup (T1) was negative control, while 2nd group (T2) was induced without any treatment (positive control), 3rd group (T3) was induction arthritis and treated with 0.2 mg/kg B.W.ofMetacam®intravenously (I/V) injection, 4th group (T4) was induced and treated with 1ml/kg of B.Wof suspension of culture mediainjected (I/V),and 5thgroup (T5) was treated withstem cellssuspension in a dose of 2.5x106 cells / ml / Kg B.W. (I/V) injection.Typical clinical signs of arthritis appeared on all induction groups.The results of Hb and RBCs showed clear reduction in all induction groups as compared with (T1), the WBCs, Erythrocyte sediment rates (ESR) and C- reactive protein (CRP) in (T2) showed clear elevation as compared with (T1), After 15 and 30 days of treatment the RBCs countand HB level showed significant decline in T2, T3and T4as compared with T5 and T1, theWBCs ,ESR and CRP significantly elevated in the T2andT4as compared with T1. The T3 and T5 showed clear depletion in levels of WBCs, ESR and CRP as compared with T2 after 15 and 30 days of treatment, while the T5 revealed no significant difference as compared with T1 after 30 days of treatment.The histopathologicalchangesin T2 and T4 showed erosion and infiltration of inflammatory cells, T3 showed hypertrophy of synovial lining and mild inflammatory cells in synovium, T5 explained return the bone tissue to normal.In this experiment concluded a successful use of stem cells in treatment of arthritis without side effect as comparison with Metacam®.

Bone marrow mesenchymal stem cell therapy for voiding dysfunction.

Lower urinary tract symptoms can significantly impact quality of life. Current standard treatments are not always effective and are associated with complications and side effects. The discovery of stem cells led to research into cell-based therapies for treatment of disorders of voiding dysfunction. Bone marrow mesenchymal stem cells are particularly promising given their ability to differentiate into a variety of cell types. Recent studies have investigated bone marrow stem cells to treat a number of functional voiding pathologies including bladder outlet obstruction, neurogenic bladder, and stress urinary incontinence. Experiments in tissue regeneration have also attempted to create artificial bladders and urethras. The purpose of this article is to critically review the literature regarding the use of bone marrow mesenchymal stem cells in treatment of voiding dysfunction.

Progress and Prospects of Stem Cells in Treatment of Drug Resistant Tuberculosis

Tuberculosis (TB) is a major cause of illness and death. The worldwide epidemic of HIV/AIDS and emergence of multidrug-resistant and extensively drug-resistant TB, are exacerbating this global public health issue. In this situation, several innovative approaches are being pursued to further improve the existing measures, as well as to identify new one. Recently, stem cell transplantation has emerged as a novel therapeutic option which holds promises for the treatment of many non-infectious and infectious diseases. Recent advances and experimental studies attracted the interest of researchers for exploring the stem cellbased treatment as a candidate treatment option for drug resistant tuberculosis. To date little has been published concerning the short and long term therapeutic effect of any type of stem cells in patients suffering from drug resistant tuberculosis. The purpose of this review is to present the viewpoints on current status and future prospect of this novel treatment approach in severe form of TB and also to discuss the opportunities and challenges associated with this approach. Keywords: Extensively drug resistant tuberculosis, multidrug resistant tuberculosis, mesenchymal stem cells, Mycobacterium tuberculosis, stem cells, tuberculosis.

Human Embryonic Stem Cells in Treatment of Spinal Cord Injury: A Prospective Study

Human Embryonic Stem Cells in Treatment of Spinal Cord Injury: A Prospective Study

Mesenchymal stem cells for treatment of experimental autoimmune encephalomyelitis and the immunoregulation mechanism

Objective To observe the efficacy of mesenchymal stem cells(MSC)for treatment of experimental autoimmune encephalomyelitis(EAE)and the related immunoregulation mechanism.Methods EAE models of C57BL/6mice were established with MOG35-55/CFA emulsion and the EAE mice were randomly divided into MSC treatment group and EAE model group.MSCs were purified and cultured from the bone marrow of GFP-C57BL/6mice.On the 15 th day of EAE model establishment,MSCs(1×106/400μL)were injected via the tail vein for the MSC treated group,and 400μL PBS were injected for the EAE model mice.Then we recorded the clinical scores and analyzed the pathological changes of spinal cord so as to evaluate the state of EAE in each group.The peripheral blood tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-4(IL-4)and transforming growth factor-β(TGF-β)cytokines were evaluated by ELISA.The percent of CD4+Foxp3+Treg cells and GFP+cells were analyzed by Flow cytometry.Results Compared with EAE model group,the MSC treated group had significantly decreased clinical score(P0.05)and less T-cell infiltration in the spinal cord.MSC treated group had increased peripheral blood IL-4,TGF-βand decreased IFN-γ,TNF-αlevels.Moreover,the MSC treated group also had greatly increased ratio of CD4+Foxp3+T cells(Treg).The MSC cells almost disappeared 10 days after transplantation.Conclusion Mesenchymal stem cell transplantation can effectively treat experimental autoimmune encephalomyelitis in mice.MSC may exert immunoregulation effect through increasing blood anti-inflammatory cytokines(IL-4,TGF-β)and decreasing proinflammatory cytokines(IFN-γ,TNF-α),which can prompt the naive cell differentiation into Treg cells.The effect of MSC remains even after disappearing for a certain time period.

Intraspinal Transplantation of Autologous Neurogenically-Induced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Paraplegic Dogs without Deep Pain Perception Secondary to Intervertebral Disk Disease.

To investigate the effects of neurogenically-induced autologous bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to intervertebral disk disease (IVDD). Seven dogs which could not be improved neurologically with conventional treatment modalities were included in the study. All dogs were diagnosed by magnetic resonance imaging and surgically treated. Each dog received two times a suspension of autologous 5.0x106 NIBM-MSCs, which were positive to CNPase and MAP-2, as well as to GFAP and beta III tubulin into the spinal cord through the hemilaminectomy defect percutaneously, with a 21-day interval. Two months after cell transplantation, there were no changes except for 1 gait score improvement for 1 of the cases. At the 4th month, gait score had improved 1 score in 5 cases, and one score progress was recorded in proprioception and nociception in 1 case. In eight months-followed up 4 cases were evaluated by the same parameter; gait score had improved in 3 cases, and propriception improved in 2 cases, and nociception improved in 3 cases. Our findings suggest that utility of autologous NIBM-MSCs for cases with poor prognosis after IVDD can be a promising approach.

Mechanism of bone marrow mesenchymal stem cells in treatment of noise induced hearing loss with intravenous transplantation

Mechanism of bone marrow mesenchymal stem cells in treatment of noise induced hearing loss with intravenous transplantation

HGFgene modified bone marrow mesenchymal stem cells for treatment of hepatic fibrosis

<i>HGF</i>gene modified bone marrow mesenchymal stem cells for treatment of hepatic fibrosis

Bone marrow mesenchymal stem cells for treatment of liver cirrhosis

Bone marrow mesenchymal stem cells for treatment of liver cirrhosis

Evaluation of mesenchymal stem cells in treatment of infertility in male rats.

IntroductionThe present study aimed to elucidate the therapeutic effects of mesenchymal stem cells (MSCs) derived from the bone marrow of rats (BM) against toxic effects of lead (Pb) on the male gonads of experimental rats.MethodsThe experimental animals were exposed to lead in the form of lead nitrate (LN) one quarter of the LD50. The efficacy of MSCs to reduce gonado-totoxicity induced by lead nitrate at 21, 30 and 60 days, was evaluated experimentally in male rats.ResultsThe results showed that testosterone levels and semen quality ameliorated following treatment with MSCs. Also, superoxide dismutase, glutathione peroxidase and catalase levels were increased 21, 30 and 60 days post treatment of MSCs. Moreover, a decrease in genomic DNA alteration and percentage of fragmented DNA was recorded after MSCs treatment. Lead nitrate caused degeneration, necrosis, interstitial edema, and reduction in spermatogenic activity in some seminiferous tubules. The LN-induced changes in histopathologic findings of testis were partially reversed by treatment with MSCs. Histological examination of testis showed deformities in morphology of testis in test animals with gross damage within the seminiferous tubules in Lead nitrate group. The LN-induced changes in histopathologic findings of testis were partially reversed by treatment of MSCs.ConclusionsIt was concluded that lead is a gonadotoxic with a tendency of suppressing semen characteristics and testosterone levels of animals, the presence of MSCs was found to alleviate the toxic effects of lead. We conclude that MSCs derived from the bone marrow of rats can be an effective therapy of LN induced gonado toxicity, thus can contribute to the treatment of infertility.

Abstract 3038: Intra-testicular transplantation of purified autologous stem cells for treatment of chemotherapy-induced male infertility

Abstract Post-chemotherapy-induced male infertility in patients with childhood cancers represents a major complication for long-term survivors. There is a significant risk for tissue damage in the seminiferous tubules, and subsequent impairment of spermatogenesis both in children and adult males who receive chemotherapy. These therapeutic regimens have deleterious effects on male fertility, resulting in the deficiency of functional spermatozoa. In adult males, fertility can be protected ahead of cancer treatment by cryopreservation of mature spermatozoa; however, this is not always possible in pre-puberty children. Autologous bone marrow stem cells (BMSCs) are suitable candidates for treating infertility after testicular exposure to low or moderate doses of chemotherapy due to their differentiation potentials into functional cell types that can promote spermatogenesis. In this report, we present a method for restoration of male fertility in post-chemotherapy cancer survivors, through intra-testicular transplantation of autologous, purified, bone marrow-derived CD34+/CD133+ stem cells. We isolated CD34+ and CD133+ cells from human bone marrow using the clinical-grade CliniMACSPLUS® Cell Purification System. CD34+/CD133+ cell populations were directly separated from MNCs collected from the bone marrow. Flow cytometry analyses for purified cell populations showed 94.5 (+3.2) % purities. CD34+/CD133+ purified populations were then injected intra-testicularly in patients on the same day of the procedure. Patients were then followed up for up to 5 years post-transplantation. No complications were reported in any patient in this study. Nine out of twenty seven patients (33%) showed pathological changes. Some cases developed spermatids in the testes (7%), while others developed fully mature spermatozoa (11%). Spermatocytes and sperms appeared in the seminal fluid in a few other cases after SCT (26%). Long term results yielded 6 natural pregnancies, 2 live births, and 1 successful IVF out of 3 (1/3) done for three couples. The advantage of using autologous adult BMSCs is in the generation of the patients' own biological offspring. Additionally these cells differentiate in vivo when placed in the gonad environment to spermatocytes, spermatids, and even mature spermatozoa. All together, this procedure minimizes the risk of genetic instability, since no propagation takes place in vitro (culture), avoids manipulation and epigenetic alteration, stabilizes the properties of the mature spermatozoa and produces a healthy offspring after transplantation. The introduction of purified, uncultured, un-manipulated, CD34+/CD133+ BMSCs into the testicles of infertile patients is a promising technique that may carry some hope for male infertility patients. Citation Format: Adeeb M. AlZoubi. Intra-testicular transplantation of purified autologous stem cells for treatment of chemotherapy-induced male infertility. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3038. doi:10.1158/1538-7445.AM2014-3038

Autologous adipose stem cells in treatment of female stress urinary incontinence: results of a pilot study.

The purpose of our study was to find out whether transurethral injections of autologous adipose stem cells (ASCs) are an effective and a safe treatment for female stress urinary incontinence (SUI). We treated five SUI patients with ASCs combined with bovine collagen gel and saline. Prior to the treatment, the ASCs were isolated from subcutaneous fat and expanded for 3 weeks in a good manufacturing practice-level laboratory. The mixture of ASCs and collagen was injected transurethrally via cystoscope. Additionally, viability, multipotency, and surface marker profile of ASCs were analyzed in vitro. We followed up with patients 3, 6, and 12 months after the injections. The primary endpoint was a cough test to measure objectively the effect of the treatment. Validated questionnaires were used to determine the subjective cure rate. After 6 months, 1 of 5 patients displayed a negative cough test with full bladder filled with 500 ml of saline. At 1 year, the cough test was negative with three patients; two of them were satisfied with the treatment and did not wish further treatment for SUI. Validated questionnaires showed some subjective improvement in all five patients. This is the first study describing the use of autologous ASCs in combination with collagen gel for female SUI treatments. Thus far, the treatment with autologous ASCs has proven safe and well tolerated. However, the feasibility and efficacy of the treatment were not optimal; therefore, additional research is needed to develop SUI injection therapies.

Using of oligodendrocyte progenitors from integration‐free human induced pluripotent stem cells in treatment of spinal cord injury (89.4)

Since the first successful derivation of induced pluripotent stem (iPS) cells, the field of regenerative medicine has grown exponentially and the goal of ‘personalized’ therapy using autologous transplants is emerging as a feasible approach. While prior studies demonstrate that human embryonic stem cells can be used to derive oligodendrocyte progenitors, there are no reports describing these cells derived from human iPS cell lines. Here, we demonstrate for the first time that oligodendrocyte progenitors (OPs) can be derived from iPS cells generated using either an episomal, non‐integrating plasmid approach or standard integrating retroviruses. The efficiency of OP differentiation ranged from 40 to 60% of total cells, which is comparable to that of human embryonic stem cells. In addition, the iPS cell lines derived using episomal vectors or retroviruses generated a similar number of early neural progenitors (NPs) and glial progenitors (GPs). We also found that the episomal plasmid‐derived iPS generated OPs expressing late OP markers (O1 and GALC), as compared to early markers (O4 and NG2), indicating that they differentiate and express mature OP markers. Moreover, we discovered that OPs derived from iPS cells engraft for over 60 days following implantation in a rat model of contusive spinal cord injury (SCI). Although further investigation is needed, these results suggest that patient‐specific, iPS‐derived OPs have potential for regenerating damaged tissue following SCI.