scholarly journals Pre-clinical Research of Human Amnion-derived Mesenchymal Stem Cells and its First Clinical Treatment for a Severe Uremic Calciphylaxis Patient

2021 ◽  
Author(s):  
Lianju Qin ◽  
Jing Zhang ◽  
Yujie Xiao ◽  
Kang Liu ◽  
Yugui Cui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Research ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Mineral Metabolism ◽  
Local Treatment ◽  
Rapid Progression ◽  
Human Amnion ◽  
Vascular Regeneration

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. We reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers and mummified legs. Because of her rapid progression and refractory to conventional therapy, human amnion-derived mesenchymal stem cells (hAMSCs) treatment was approved. Establishment and release inspection of hAMSCs, efficacy and safety assessment including cytokines secretory ability, immunocompetence, tumorigenicity and genetics analysis in vitro were introduced. We further performed acute and long-term hAMSC toxity evaluations in C57BL/6 mice/rats, abnormal immune response tests in C57BL/6 mice and tumorigenic tests in the neonatal NU nude mice. After pre-clinical research, she was treated by hAMSCs with intravenous and local intramuscular injection and external supernatants application to her ulcers. When followed up to 15 months, her blood-based markers of bone and mineral metabolism were improved, with regeneration of skin soft tissue and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1 month treatment showed vascular regeneration with mature non-calcified vessels within dermis and 20 months later re-epithelialization restored the integrity of damaged site. No infusion or local treatment related adverse events occurred. To the best of our knowledge, this is the first evidence for the clinical use of hAMSCs. These findings suggest hAMSCs warrant further investigation as a potential regenerative treatment for uremic calciphylaxis with effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multi-differentiation, re-epithelialization and restorage of integrity.

Potential Role of Immunosuppression in Therapeutic Effects Conferred by Cord Blood- Derived Mesenchymal Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2302-2302
Author(s):  
Nagwa S. El-Badri (Dajani) ◽  
Denis English ◽  
Amal Hakki ◽  
Sriram Mudhusoodanan ◽  
Cyndy D. Sanberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Cord Blood ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Peripheral Blood Mononuclear ◽  
Murine Splenocytes

Abstract Our previous studies consistently demonstrate enhanced neural protective effects of cord blood in comparison to stem cells from adult marrow. Similarly, cord blood possesses diminished immuno-stimulatory activity, and the basis of this effect has not been defined. Since neural damage may be potentiated by immune activation of inflammatory cascades, we examined the effects of cord blood-derived MSCs (mesenchymal stem cells) on immune responses. We isolated and characterized a population of cord blood MSCs. These cells maintained their pluripotency in culture. Progeny generated in the absence of differentiation were strongly adherent, did not express CD34, CD45, CD3, CD19 antigens, and did not generate hematopoietic colonies in methylcellulose. However, cultured cord blood MSCs possessed a remarkable ability to support the proliferation as well as the differentiation of hematopoietic cells in vitro. In addition, supernatants from cultured cord blood MSCs promoted survival of peripheral blood mononuclear cells cultured under conditions designed to induce cell stress and limit protein synthesis. We examined immune modulation by cord blood MSCs after co-culture with murine splenocytes. While spleen cells from normal C57Bl/6 mice exhibited a prominent IgM response after immunization with the T-cell dependent antigen, SRBCs, this response was significantly decreased after incubation with cord blood MSCs. Consistently, cord blood MSCs mitigated the enhanced mixed lymphocyte proliferative response C57Bl/6 T-cells exhibit when exposed to lymphocytes from non-related animals. To investigate whether these immune suppressive properties could be therapeutically useful in a transplantation model for autoimmune disease, cord blood MSCs were transplanted into sublethally irradiated BXSB mouse model for systemic lupus. Thirty days after infusion, defective IgM humoral immune responses of splenocytes of these mice normalized. This normalization paralleled normalization of the disrupted lymphoid cellularity observed in the spleens of diseased animals. Our results are consistent with the hypothesis that immune regulation is involved in the therapeutic utility of MSCs.

Biological Aspects and Clinical Applications of Mesenchymal Stem Cells: Key Features You Need to be Aware of.

2020 ◽  
Vol 21 ◽  
Author(s):  
Mohammad Saeedi ◽  
Muhammad Sadeqi Nezhad ◽  
Fatemeh Mehranfar ◽  
Mahdieh Golpour ◽  
Mohammad Ali Esakandari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Immune Modulation ◽  
Adult Stem Cells ◽  
Inflammatory Diseases ◽  
High Capacity ◽  
Genetically Engineered ◽  
Cartilage Cells ◽  
Biological Aspects

: Mesenchymal stem cells (MSCs), a form of adult stem cells, are known to have a self-renewing property and the potential to specialize into a multitude of cells and tissues such as adipocytes, cartilage cells, and fibroblasts. MSCs can migrate and home to the desired target zone where inflammation is present. The unique characteristics of MSCs in repairing, differentiation, regeneration, and its high capacity of immune modulation has attracted tremendous attention for exerting them in clinical purposes, as they contribute to tissue regeneration process and anti-tumor activity. The MSCs-based treatment has demonstrated remarkable applicability towards various diseases such as heart and bone malignancies, and cancer cells. Importantly, genetically engineered MSCs, as a state-of-the-art therapeutic approach, could address some clinical hurdles by systemic secretion of cytokines and other agents with a short half-life and high toxicity. Therefore, understanding the biological aspects and the characteristics of MSCs is an imperative issue of concern. Herein, we provide an overview of the therapeutic application and the biological features of MSCs against different inflammatory diseases and cancer cells. We further shed light on MSCs physiological interaction, such as migration, homing, and tissue repairing mechanisms with different healthy and inflamed tissues.

scholarly journals Tailored Hydrogels as Delivery Platforms for Conditioned Medium from Mesenchymal Stem Cells in a Model of Acute Colitis in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1127
Author(s):  
Juan Sendon-Lago ◽  
Lorena Garcia-del Rio ◽  
Noemi Eiro ◽  
Patricia Diaz-Rodriguez ◽  
Leandro Avila ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Conditioned Medium ◽  
Local Treatment ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Acute Colitis ◽  
Tnf Α ◽  
Ifn Γ

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.

scholarly journals Bone remodeling using a three-dimensional chitosan - hydroxyapatite scaffold seeded with hypoxic conditioned human amnion mesenchymal stem cells

2021 ◽  
Vol 54 (2) ◽  
pp. 68
Author(s):  
Michael Josef Kridanto Kamadjaja
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Remodeling ◽  
Three Dimensional ◽  
Wistar Rat ◽  
Control Group ◽  
Human Amnion ◽  
Morphogenetic Protein ◽  
Hydroxyapatite Scaffold ◽  
Endothelial Growth Factor

Background: Bone regeneration studies involving the use of chitosan–hydroxyapatite (Ch-HA) scaffold seeded with human amnion mesenchymal stem cells (hAMSCs) have largely incorporated tissue engineering experiments. However, at the time of writing, the results of such investigations remain unclear. Purpose: The aim of this study was to determine the osteogenic differentiation of the scaffold Ch-HA that is seeded with hAMSCs in the regeneration of calvaria bone defect. Methods: Ch-HA scaffold of 5 mm diameter and 2 mm height was created by lyophilisation and desalination method. hAMSCs were cultured in hypoxia environment (5% oxygen, 10% carbon dioxide, 15% nitrogen) and seeded on the scaffold. Twenty male Wistar rat subjects (8 – 10 weeks, 200 - 250 grams) were randomly divided into two groups: control and hydroxyapatite scaffold (HAS). Defects (similar size to scaffold size) were created in the calvaria bone of the all-group subjects, but a scaffold was subsequently implanted only in the treatment group members. Control group left without treatment. After observation lasting 1 and 8 weeks, the subjects were examined histologically and immunohistochemically. Statistical analysis was done using ANOVA test. Results: Angiogenesis; expression of vascular endothelial growth factor; bone morphogenetic protein; RunX-2; alkaline phosphatase; type-1 collagen; osteocalcin and the area of new trabecular bone were all significantly greater in the HAS group compared to the control group. Conclusion: The three-dimensional Ch-HA scaffold seeded with hypoxic hAMSCs induced bone remodeling in calvaria defect according to the expression of the osteogenic and angiogenic marker.

scholarly journals Possibilities of using allogeneic mesenchymal stem cells and wound dressings based on aliphatic copolyamide in microautodermoplasty

2020 ◽  
Vol 8 (2) ◽  
pp. 185-196
Author(s):  
Vasily A. Gordienko ◽  
Evgenii V. Zinoviev ◽  
Denis V. Kostyakov ◽  
Marat S. Asadulaev ◽  
Anton S. Shabunin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Medicine ◽  
Medical Science ◽  
Local Treatment ◽  
Treatment Algorithm ◽  
Wound Dressings ◽  
Results Of Treatment ◽  
Healing Index ◽  
Treatment Of Wounds

Background. The treatment of victims with wound defects is an urgent problem of clinical medicine that doctors of various specialties, mainly surgeons and traumatologists, must face. Regardless of the etiology of the traumatic agent, the wound process is always subjected to fundamental pathophysiological processes. Despite the advances made by medical science in the local treatment of wounds (cell technology, modern wound coverings, and others), surgical procedures remain the main methods, and the search for new techniques to optimize reparative regeneration continues. This ongoing search indicates the absence of a universal algorithm for treating such defects. This lack of a universal treatment algorithm is of particular importance for assisting victims with extensive defects, which often leads to a shortage of donor resources. Aim. The aim of this study was to increase the efficiency of microautodermoplasty due to the use of allogeneic mesenchymal stem cells and wound dressings based on aliphatic copolyamide. Materials and methods. This paper presents the results of an experimental study involving 50 rats. All animals were divided into groups considering the choice of the method of the local treatment. The experimental wound was modeled according to its original technique. The evaluation of the effectiveness of the analyzed methods was performed using planimetric and histological research methods, and by calculating the healing index. Results. The most effective methods for treating experimental wounds using microautodermoplasty (MADP) are wound dressings based on aliphatic copolyamide (CoPA) and adipogenic mesenchymal stem cells (AMSC). By 28 days of treatment after performing MADP + CoPA wound dressings + AMSC, it was possible to reduce the defect area by 16 times compared with the control, and the healing index was the maximum value among all methods 12.5 units. The high regenerative potential was also confirmed by the results of the histological examination. The worst results were found in the MADP group with AMSK that did not cover the wounds with skin or wound dressing. Conclusion. The introduction of the analyzed methods into clinical practice will improve the results of treatment of patients with wound defects of various etiologies.

scholarly journals The Comparison of the Immunologic Properties of Stem Cells Isolated from Human Exfoliated Deciduous Teeth, Dental Pulp, and Dental Follicles

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Selin Yildirim ◽  
Noushin Zibandeh ◽  
Deniz Genc ◽  
Elif Merve Ozcan ◽  
Kamil Goker ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Venous Blood ◽  
Deciduous Teeth ◽  
Peripheral Blood Mononuclear ◽  
Human Exfoliated Deciduous Teeth

Aim. To compare the effects of various mesenchymal stem cells, those isolated from human exfoliated deciduous teeth (SHEDs), dental pulp stem cells (DPSCs), and dental follicle stem cells (DFSCs), on human peripheral blood mononuclear cells (PBMCs).Method. Mesenchymal stem cells were isolated from three sources in the orofacial region. Characterization and PCR analyses were performed. Lymphocytes were isolated from healthy peripheral venous blood. Lymphocytes were cocultured with stem cells in the presence and absence of IFN-γand stimulated with anti-CD2, anti-CD3, and anti-CD28 for 3 days. Then, lymphocyte proliferation, the number of CD4+FoxP3+T regulatory cells, and the levels of Fas/Fas ligand, IL-4, IL-10, and IFN-γin the culture supernatant were measured.Results. The DFSCs exhibited an enhanced differentiation capacity and an increased number of CD4+FoxP3+T lymphocytes and suppressed the proliferation and apoptosis of PBMCs compared with SHEDs and DPSCs. The addition of IFN-γaugmented the proliferation of DFSCs. Furthermore, the DFSCs suppressed IL-4 and IFN-γcytokine levels and enhanced IL-10 levels compared with the other cell sources.Conclusion. These results suggest that IFN-γstimulates DFSCs by inducing an immunomodulatory effect on the PBMCs of healthy donors while suppressing apoptosis and proliferation and increasing the number of CD4+FoxP3+cells.

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