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Stemcell Research & Evidence - Auto-Immune Diseases

New Zealand Stem Cell Therapy Auckland & Christchurch

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New Zealand Stem Cell Clinic Auckland & Christchurch

Safety and Efficacy of Stromal Vascular Fraction Enriched Fat Grafting Therapy for Vulvar Lichen Sclerosis

Cureus. 2020 Feb; 12(2): e7096.


Plastic Surgery, Hospital La Luz, Madrid, ESP.



BackgroundLichen sclerosus is an inflammatory dermatosis of unknown etiology which currently has no cure. Most treatment guidelines recommend the use of ultrapotent topical corticosteroids. However, the relapse rate is usually high. Through a retrospective study we evaluated the efficacy and safety of stromal vascular fraction of adipose tissue as therapy for lichen sclerosus.


Material and methods: For this retrospective review, we obtained data on patients with vulvar lichen sclerosus treated with autologous fat grafting enriched with adipose derived stromal vascular fraction cells. Data collected through a modified vulvo-vaginal symptoms questionnaire were analyzed before treatment, six months and 24 months after treatment. The 19 items questionnaire was subdivided in four categories: symptoms, signs, social functioning and sexual functioning. Global scores and partial scores for each category were analyzed using paired t-test. For all statistical analyses, a value of p ≤ 0.05 was considered statistically significant. All data are presented as mean ± SD.


Results: Thirty nine patients were included in the study. Thirty seven patients (94.87%) experienced a significant decrease in global score at six months and 24 months after treatment (p < 0.05). Decrease in scores were also statistically significant between pretreatment and 24 months after treatment for each of the four questionnaire categories - symptoms, signs, social functioning and sexual functioning (p < 0.05).


Conclusions: This retrospective study showed that the use of autologous fat grafting enriched with adipose derived stromal vascular fraction is safe and leads to significant and long lasting improvement in patients with vulvar lichen sclerosus.

Cell therapy for cardiac repair

Br Med Bull. 2010;94:65-80.


Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, Middlesex, UB9 6JH, UK.


Heart failure is a leading cause of morbidity and mortality worldwide. The current strategies for treatment are limited and new therapeutic approaches are needed. This review describes research performed in animal models of cardiac disease and clinical trials and discusses the mechanisms involved in possible beneficial effects of cell therapy. Cell therapy is a promising strategy to treat heart failure, as it aims to replenish the failing myocardium with contractile elements. However, cell therapy with adult progenitor cells induces a small improvement in heart function without significant cardiomyogenesis. Paracrine mechanisms are likely to be important. The most effective cell type for therapy remains unclear. Induced pluripotent stem cells have the greatest potential but more information on the properties of this cell type is needed. The integration of cells in the host myocardium and the routes of delivery remain controversial. The differentiation of cardiac cells from pluri- and multipotent cells and the understanding of their properties are growing points in cell therapy. More research is needed to correctly assess the physiological properties of differentiating cells, to dissect the role of the host environment in the integration and differentiation and to define the stage of differentiation required for cell transplantation.

Intracoronary and intramyocardial stem cell therapy of the heart

J Am Coll Cardiol. 2011 Sep 6;58(11):1095-104.


Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany.


Intracoronary and intramyocardial stem cell therapy aim at the repair of compromised myocardium thereby--as a causal treatment--preventing ventricular remodeling and improving overall performance. Since the first-in-human use of bone marrow stem cells (BMCs) after acute myocardial infarction in 2001, a large number of clinical studies have demonstrated their clinical benefit: BMC therapy can be performed with usual cardiac catheterization techniques in the conscious patient as well as also easily during cardiosurgical interventions. New York Heart Association severity degree of patients as well as physical activity improve in addition to ("on top" of) all other therapeutic regimens. Stem cell therapy also represents an ultimate approach in advanced cardiac failure. For acute myocardial infarction and chronic ischemia, long-term mortality after 1 and 5 years, respectively, is significantly reduced. A few studies also indicate beneficial effects for chronic dilated cardiomyopathy. The clinical use of autologous BMC therapy implies no ethical problems, when unmodified primary cells are used. With the use of primary BMCs, there are no major stem cell-related side effects, especially no cardiac arrhythmias and inflammation. Various mechanisms of the stem cell action in the human heart are discussed, for example, cell transdifferentiation, cell fusion, activation of intrinsic cardiac stem cells, and cytokine-mediated effects. New techniques allow point-of-care cell preparations, for example, within the cardiac intervention or operation theater, thereby providing short preparation time, facilitated logistics of cell transport, and reasonable cost effectiveness of the whole procedure. The 3 main indications are acute infarction, chronic ischemic heart failure, and dilated cardiomyopathy. Future studies are desirable to further elucidate the mechanisms of stem cell action and to extend the current use of intracoronary and/or intramyocardial stem cell therapy by larger and presumably multicenter and randomized trials.

Mesenchymal stem cells: ideal seeds for treating diseases

Hum Cell. 2021; 34(6): 1585–1600.


School of Laboratory Medicine, The First Affiliated Hospital, Bengbu Medical College, Bengbu, China


Mesenchymal stem cells (MSCs), a kind of multipotent stem cells with self-renewal ability and multi-differentiation ability, have become the “practical stem cells” for the treatment of diseases. MSCs have immunomodulatory properties and can be used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and Crohn’s disease. MSCs also can be used in cancer and aging. At present, many clinical experiments are using MSCs. MSCs can reduce the occurrence of inflammation and apoptosis of tissue cells, and promote the proliferation of endogenous tissue and organ cells, so as to achieve the effect of repairing tissue and organs. MSCs presumably also play an important role in Corona Virus Disease 2019 (COVID-19) infection.

Efficacy of stem cells therapy for Crohn’s fistula

Stem Cell Res Ther. 2021; 12: 32.


Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, 453003 Henan Province China


Background: Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn’s fistula.

Methods: Electronic databases were searched comprehensively for studies reporting the efficacy and safety of stem cells in patients with any form of Crohn’s fistula. A random-effects model was used, and all outcomes were calculated by SPSS 24.0.

Results: Twenty-nine articles with 1252 patients were included. It showed that stem cell group had a higher rate of fistula healing compared to placebo group in patients of Crohn’s fistula (61.75% vs 40.46%, OR 2.21, 95% CI 1.19 to 4.11, P < 0.05). 3 × 107 cells/mL stem cell (SC) group had an advantage in fistula healing rate with 71.0% compared to other doses group of stem cells (RR 1.3, 95% CI 0.76 to 2.22). And the healing rates of patients with perianal and transsphincteric fistulas (77.95%, 76.41%) were higher than those with rectovaginal fistulas. It was an amazing phenomenon that CDAI and PDAI scores occurred an obviously transient rise with the use of stem cells after 1 month (both of P < 0.05), while they returned to the baseline level by giving stem cells 3 months later. Furthermore, the incidence rate of treatment-related adverse events in the stem cell group was significantly lower than in the placebo group (RR 0.58, 95% CI 0.30 to 1.14).

Conclusions: Our study has highlighted that stem cells was a promising method in the treatment of Crohn’s fistula based on its higher efficacy and lower incidence of adverse events, especially ADSCs and Cx601. While it also needs more clinical and pre-clinical studies to strengthen evidences in the future.

Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn’s Disease

Int J Mol Sci. 2021 Sep; 22(18): 9967.


Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France.


Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.

Mesenchymal Stem Cells for Perianal Crohn's Disease

Cells. 2019 Jul 23;8(7):764.


Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, 20089 Rozzano, Italy.


Perianal fistulizing Crohn's disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two decades, the management of PFCD has evolved in terms of the multidisciplinary approach involving gastroenterologists and colorectal surgeons. However, the highest fistula healing rates, even combining surgical and anti-TNF agents, reaches 50% of treated patients. More recently, the administration of mesenchymal stem cells (MSCs) have shown notable promising results in the treatment of PFCD. The aim of this review is to describe the rationale and the possible mechanism of action of MSC application for PFCD and the most recent results of randomized clinical trials. Furthermore, the unmet needs of the current administration process and the expected next steps to improve the outcomes will be addressed.

Stem cell therapy for Crohn's disease

Stem Cell Res Ther. 2021 Aug 18;12(1):463.


State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City, 310003, China.



Background: We explored whether stem cell therapy was effective for animal models and patients with Crohn's disease (CD).


Methods: We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality.


Results: We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD - 4.58, p = 0.000; rats: SMD - 1.41, P = 0.000) and lower myeloperoxidase levels (SMD - 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD - 2.10, P = 0.000), the CD endoscopic index of severity (SMD - 3.40, P = 0.000) and simplified endoscopy score for CD (SMD - 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3-24 months after transplantation.


Conclusions: Stem cell transplantation is a valuable supplementary therapy for CD.

Novel approaches in the treatment of myositis and myopathies

Ther Adv Musculoskelet Dis. 2012 Oct; 4(5): 369–377.


Jemima Albayda, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA


The inflammatory myopathies are a heterogeneous group of disorders characterized by muscle weakness and inflammation. Although no standard therapeutic guidelines exist, traditional treatment has included corticosteroids and a variety of second-line immunosuppressants. As treatment of refractory disease has been difficult, newer agents and approaches have been used with varying response. The advent of standardized treatment response criteria by the International Myositis Assessment and Clinical Studies (IMACS) group has helped investigators to evaluate and compare clinical trial outcomes in a more rigorous fashion. The use of intravenous immunoglobulin (IVIG), rituximab, biologic agents including tumor necrosis factor (TNF) inhibitors, stem-cell transplantation, gene therapy, and vascular occlusion resistance training are reviewed here. As our understanding of disease pathogenesis at the immunologic, genetic, and molecular level expands, the discovery of novel therapeutic targets hold promise for the successful treatment of these conditions.

Impact of adipose-derived stem cells injection in a mouse model of inclusion body myositis





Sporadic inclusion body myositis (sIBM) is the most common myopathy after age 45. It is a progressive disease with a severe prognosis leading to wheelchair confinement in ten years from the onset. So far no treatment has yet been shown to slow or stop the progression of the disease. sIBM involves both inflammatory and degenerative characteristics, and the true primary pathogenesis of the disease remains a subject of intense debate. From a cellular point of view, it has been shown that although satellite cells (SC) proliferation is normal in IBM patients, their differentiation ability is impaired, leading to muscle regeneration program failure. Interestingly fibro-adipogenic progenitors (FAP) which have been recently identified in muscle exhibit an essential supportive role for effective muscle regeneration and have never been studied in the context of sIBM. However, FAP are similar to adipose-derived stem cells (ASC) which have become an attractive multipotent cell population for use in regenerative medicine. Our hypothesis is that FAP number and/or function are altered in IBM and that ASC injection might prevent muscle degeneration in sIBM.Based on human chloroquine-induced myopathy, a mouse model of sIBM was settled using oral administration of chloroquine for 20 weeks. Mice were assigned to three groups: control mice, mice treated with chloroquine receiving or not intramuscular injections of ASC. A global follow-up of the animals was performed during 20 weeks, including muscle strength evaluation, muscle ultrasound analysis, flow cytometry analysis of the muscles, stem cell function evaluation (colony-forming unit fibroblasts (CFU-F) assay) and histology. Our results show that chloroquine-treated mice exhibit myopathy symptoms which are associated with modifications of both FAP and satellite cell content and functions. Besides, intramuscular ASC injections seem to improve muscle strength compared to chloroquine-treated mice.In conclusion, while preliminary our results strongly suggest that intramuscular injections of ASC might be a promising therapeutic option.

Mesenchymal stem/stromal cell-based therapy for the treatment of rheumatoid arthritis

EBioMedicine. 2021 Jul;69:103427.


Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER), Madrid; Spain; Advanced Therapy Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD/UAM). Electronic address:


Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and progressive joint destruction and is a primary cause of disability worldwide. Despite the existence of numerous anti-rheumatic drugs, a significant number of patients with RA do not respond or are intolerant to current treatments. Mesenchymal stem/stromal cell (MSCs) therapy represents a promising therapeutic tool to treat RA, mainly attributable to the immunomodulatory effects of these cells. This review comprises a comprehensive analysis of the scientific literature related to preclinical studies of MSC-based therapy in RA to analyse key aspects of current protocols as well as novel approaches which aim to improve the efficacy of MSC-based therapy.

Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis

Int J Mol Sci. 2021 Oct 27;22(21):11592.


Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan 010000, Kazakhstan.


Mesenchymal stem cells (MSCs) have great potential to differentiate into various types of cells, including but not limited to, adipocytes, chondrocytes and osteoblasts. In addition to their progenitor characteristics, MSCs hold unique immunomodulatory properties that provide new opportunities in the treatment of autoimmune diseases, and can serve as a promising tool in stem cell-based therapy. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that deteriorates quality and function of the synovium membrane, resulting in chronic inflammation, pain and progressive cartilage and bone destruction. The mechanism of RA pathogenesis is associated with dysregulation of innate and adaptive immunity. Current conventional treatments by steroid drugs, antirheumatic drugs and biological agents are being applied in clinical practice. However, long-term use of these drugs causes side effects, and some RA patients may acquire resistance to these drugs. In this regard, recently investigated MSC-based therapy is considered as a promising approach in RA treatment. In this study, we review conventional and modern treatment approaches, such as MSC-based therapy through the understanding of the link between MSCs and the innate and adaptive immune systems. Moreover, we discuss recent achievements in preclinical and clinical studies as well as various strategies for the enhancement of MSC immunoregulatory properties.

Immunomodulatory Effects of Mesenchymal Stem Cells and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Rheumatoid Arthritis

Front Immunol. 2020 Aug 20;11:1912.


Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.


Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints and other organs for which there is currently no effective treatment. Mesenchymal stem cells (MSCs) have therapeutic potential due to their immunomodulatory and differentiation effects. While extensive experimental studies and clinical trials have demonstrated the effects of MSCs in various diseases, MSCs have been found to cause abnormal differentiation and tumor formation. Therefore, extracellular vesicles derived from MSCs (MSC-EVs) are more effective, less toxic, and more stable than the parental cells. MSC-EVs transfer various nucleic acids, proteins, and lipids from parent cells to recipient cells, and thus participate in chronic inflammatory and immune processes. In this review, we summarize the properties and biological functions of MSCs and MSC-EVs in RA. Improvement in our understanding of the mechanisms underlying MSC and MSC-EVs in RA provides an insight into potential biomarkers and therapeutic strategies for RA.

Mesenchymal Stem Cells Improve Rheumatoid Arthritis Progression by Controlling Memory T Cell Response

Front Immunol. 2019 Apr 16;10:798.


Laboratorio de Inmunología Celular y Molecular, Centro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.


In the last years, mesenchymal stem cell (MSC)-based therapies have become an interesting therapeutic opportunity for the treatment of rheumatoid arthritis (RA) due to their capacity to potently modulate the immune response. RA is a chronic autoimmune inflammatory disorder with an incompletely understood etiology. However, it has been well described that peripheral tolerance defects and the subsequent abnormal infiltration and activation of diverse immune cells into the synovial membrane, are critical for RA development and progression. Moreover, the imbalance between the immune response of pro-inflammatory and anti-inflammatory cells, in particular between memory Th17 and memory regulatory T cells (Treg), respectively, is well admitted to be associated to RA immunopathogenesis. In this context, MSCs, which are able to alter the frequency and function of memory lymphocytes including Th17, follicular helper T (Tfh) cells and gamma delta (γδ) T cells while promoting Treg cell generation, have been proposed as a candidate of choice for RA cell therapy. Indeed, given the plasticity of memory CD4+ T cells, it is reasonable to think that MSCs will restore the balance between pro-inflammatory and anti-inflammatory memory T cells populations deregulated in RA leading to prompt their therapeutic function. In the present review, we will discuss the role of memory T cells implicated in RA pathogenesis and the beneficial effects exerted by MSCs on the phenotype and functions of these immune cells abnormally regulated in RA and how this regulation could impact RA progression.

Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients

Drug Des Devel Ther. 2019 Dec 19;13:4331-4340.


Cell Therapy Center, 986 Hospital of People's Liberation Army Air Force, Xi'an, Shaanxi, People's Republic of China.


Background: The traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA.

Methods: 64 RA patients aged 18-64 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 × 107 cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy.

Results: 1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05).

Conclusion: UC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.

Chondrogenic potential of mesenchymal stem cells from patients with rheumatoid arthritis and osteoarthritis

Cells Tissues Organs. 2009;189(5):307-16.


Polyclinic of the Hospitaller Brothers of St. John of God, Budapest, Hungary.


Background: Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct mesenchymal tissues; including cartilage and bone, they can be an attractive cell source for cartilage tissue engineering approaches. Our objective here was to compare the in vitro chondrogenic potential of MSCs isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) with cells from normal donors.

Methods: Marrow samples were removed during bone surgery and adherent cell cultures were established. The cells were then passed into a newly developed microaggregate culture system in a medium containing transforming growth factor beta3, insulin, dexamethasone and/or demineralized bone matrix. In vitro chondrogenic activity was measured as metabolic sulfate incorporation and type II collagen expression in pellet cultures.

Results: Culture-expanded MSCs from RA and OA patients did not differ significantly from the normal population with respect to their chondrogenic potential in vitro. Capability of total protein and proteoglycan synthesis as well as collagen II mRNA expression by cell aggregates was similar for all cell preparations in the presence of the appropriate growth and differentiation factors. Chondroprotective drugs such as chondroitin sulfate and glucosamine enhanced, whereas chloroquine inhibited chondrogenesis in normal donor-derived or patient-derived MSC cultures. Galectin-1, a beta-galactoside-binding protein with marked anti-inflammatory activity, stimulated the chondrogenic differentiation of mesenchymal cells in low (<2 microg/ml) concentration.

Discussion: These findings show that MSCs from RA and OA patients possess similar chondrogenic potential as MSCs isolated from healthy donors, therefore these cells may serve as a potential new prospect in cartilage replacement therapy.

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