The Immunomodulatory Effects of Mesenchymal Stem Cells in Prevention or Treatment of Excessive Scars

Excessive scars, including keloids and hypertrophic scars, result from aberrations in the process of physiologic wound healing. An exaggerated inflammatory process is one of the main pathophysiological contributors. Scars may cause pain, and pruritis, limit joint mobility, and cause a range of cosmetic deformities that affect the patient’s quality of life. Extensive research has been done on hypertrophic scar and keloid formation that has resulted in the plethora of treatment and prevention methods practiced today. Mesenchymal stem cells, among their multifunctional roles, are known regulators of inflammation and have been receiving attention as a major candidate for cell therapy to treat or prevent excessive scars. This paper extensively reviews the body of research examining the mechanism and potential of stem cell therapy in the treatment of excessive scars.

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Mesenchymal Stem Cells and Clinical Application in Chronic Lung Diseases

Jurnal Respirasi ◽

10.20473/jr.v7-i.3.2021.145-151 ◽

2021 ◽

Vol 7 (3) ◽

pp. 145

Author(s):

Isti Mardiana Soetartio ◽

Triya Damayanti

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Clinical Application ◽

The Body ◽

Hematopoietic Stem ◽

Chronic Lung Diseases ◽

Practice Approach ◽

Drug Manufacturing ◽

Respiratory Area

Mesenchymal stem cells are a multipotent mature non hematopoietic stem cells, with characteristics such as ability to self-renew and differentiate in mesodermal, ectodermal, and endodermal pathway. Mesenchymal stem cells also secrete cytokine and immunoreceptor which regulate micro environment in host tissues and angiogenic mediators which are able to improve damaged tissues. Mesenchymal stem cells are obtained from the human body by isolation, culture, proliferation, characterization, and/or differentiation originating from fat cells (adipose), periosteum tissue, and other tissues from the body. Mesenchymal stem cells can be obtained by autologous and allogenic way. Stem cell processing includes isolation, proliferation, differentiation, and temporary storage for clinical application adhering to good drug manufacturing practice. Approach to cell therapy and bioengineering in lung disease is rapidly developing in the last 10 years. In the current era of cell therapy and transplantation, a lot of research has been done to understand and develop mesenchymal stem cells as a therapeutic alternative, particularly in respiratory area.

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Placenta-derived mesenchymal stem cells for allogenic cardiac cell therapy

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0031-1297675 ◽

2012 ◽

Vol 60 (S 01) ◽

Cited By ~ 1

Author(s):

R Roy ◽

M Kukucka ◽

D Messroghli ◽

A Brodarac ◽

M Becher ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Cardiac Cell ◽

Cardiac Cell Therapy

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Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

Perspectives in Surgery ◽

10.33699/pis.2019.98.9.350-355 ◽

2019 ◽

Vol 98 (9) ◽

pp. 350-355

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Portal Vein ◽

Liver Parenchyma ◽

Miniature Pig ◽

Hepatic Diseases ◽

Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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Innovative Cell Therapy in the Treatment of Serious Adverse Events Related to Both Chemo-Radiotherapy Protocol and Acute Myeloid Leukemia Syndrome: The Infusion of Mesenchymal Stem Cells Post-Treatment Reduces Hematopoietic Toxicity and Promotes Hematopoietic Reconstitution

Current Pharmaceutical Biotechnology ◽

10.2174/1389201014666131227120222 ◽

2014 ◽

Vol 14 (9) ◽

pp. 842-848 ◽

Cited By ~ 10

Author(s):

Loic Fouillard ◽

Sabine Francois ◽

Sandrine Bouchet ◽

Morad Bensidhoum ◽

Abdelatif Elm’selmi ◽

...

Keyword(s):

Stem Cells ◽

Acute Myeloid Leukemia ◽

Mesenchymal Stem Cells ◽

Adverse Events ◽

Cell Therapy ◽

Myeloid Leukemia ◽

Serious Adverse Events ◽

Hematopoietic Reconstitution ◽

Hematopoietic Toxicity ◽

Acute Myeloid

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Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽

10.3390/biomedicines9060667 ◽

2021 ◽

Vol 9 (6) ◽

pp. 667

Author(s):

Gabriella Racchetti ◽

Jacopo Meldolesi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Responses ◽

Extracellular Vesicles ◽

Immune Regulation ◽

Great Increase ◽

The Body ◽

Cell Aging ◽

Therapeutic Effects ◽

Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

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Mesenchymal Stem Cells in the Treatment of Cartilage Defects of the Knee: A Systematic Review of the Clinical Outcomes

The American Journal of Sports Medicine ◽

10.1177/0363546520986812 ◽

2021 ◽

pp. 036354652098681

Author(s):

Monketh Jaibaji ◽

Rawan Jaibaji ◽

Andrea Volpin

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Osteochondral Lesions ◽

Common Source ◽

Significant Heterogeneity ◽

Osteochondral Defects

Background: Osteochondral lesions are a common clinical problem and their management has been historically challenging. Mesenchymal stem cells have the potential to differentiate into chondrocytes and thus restore hyaline cartilage to the defect, theoretically improving clincal outcomes in these patients. They can also be harvested with minimal donor site morbidity. Purpose: To assess the clinical and functional outcomes of mesenchymal stem cell implantation to treat isolated osteochondral defects of the knee. A secondary purpose is to assess the quality of the current available evidence as well as the radiological and histological outcomes. We also reviewed the cellular preparation and operative techniques for implantation. Study Design: Systematic review. Methods: A comprehensive literature search of 4 databases was carried out: CINAHL, Embase, MEDLINE, and PubMed. We searched for clinical studies reporting the outcomes on a minimum of 5 patients with at least 12 months of follow-up. Clinical, radiological, and histological outcomes were recorded. We also recorded demographics, stem cell source, culture technique, and operative technique. Methodological quality of each study was assessed using the modified Coleman methodology score, and risk of bias for the randomized controlled studies was assessed using the Cochrane Collaboration tool. Results: Seventeen studies were found, encompassing 367 patients. The mean patient age was 35.1 years. Bone marrow was the most common source of stem cells utilized. Mesenchymal stem cell therapy consistently demonstrated good short- to medium-term outcomes in the studies reviewed with no serious adverse events being recorded. There was significant heterogeneity in cell harvesting and preparation as well as in the reporting of outcomes. Conclusion: Mesenchymal stem cells demonstrated a clinically relevant improvement in outcomes in patients with osteochondral defects of the knee. More research is needed to establish an optimal treatment protocol, long-term outcomes, and superiority over other therapies. Registration: CRD42020179391 (PROSPERO).

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Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02110-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pegah Nammian ◽

Seyedeh-Leili Asadi-Yousefabad ◽

Sajad Daneshi ◽

Mohammad Hasan Sheikhha ◽

Seyed Mohammad Bagher Tabei ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Cell Therapy ◽

Femoral Artery ◽

Critical Limb Ischemia ◽

Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

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Intravenous Administration of Human Amniotic Mesenchymal Stem Cells in the Subacute Phase of Cerebral Infarction in a Mouse Model Ameliorates Neurological Disturbance by Suppressing Blood Brain Barrier Disruption and Apoptosis via Immunomodulation

Cell Transplantation ◽

10.1177/09636897211024183 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110241

Author(s):

Yasunori Yoshida ◽

Toshinori Takagi ◽

Yoji Kuramoto ◽

Kotaro Tatebayashi ◽

Manabu Shirakawa ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mouse Model ◽

Cerebral Infarction ◽

Blood Brain Barrier ◽

Brain Infarction ◽

Brain Barrier ◽

Neurological Deficits ◽

Immunomodulatory Effects ◽

Amniotic Mesenchymal Stem Cells

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

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