Asthma immunotherapy and treatment approaches with mesenchymal stem cells

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 665-674
Author(s):  
Tunç Akkoç ◽  
Deniz Genç

Asthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1133
Author(s):  
Marcin Włodarczyk ◽  
Katarzyna Czerwińska ◽  
Jakub Włodarczyk ◽  
Jakub Fichna ◽  
Adam Dziki ◽  
...  

Perianal fistula in patients with Crohn’s disease is an extremely challenging condition. The disease tends to reoccur, and with current treatment options, a large number of patients are left with active ailment and experience major morbidity. In recent years, hopeful results regarding local use of mesenchymal stem cells (MSCs) in perianal Crohn’s disease have been published. Although to this day there are no clear guidelines determining optimal dosage, injections frequency and culture conditions, their efficiency has proven to be much higher than conventionally used methods. According to studies, they can effectively induce as well as maintain fistula closure. This approach also avoids common side effects related to conventional surgical treatment.


2019 ◽  
Vol 8 (9) ◽  
pp. 1413 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Maciej Banach ◽  
Željko Reiner ◽  
Matteo Pirro ◽  
Saeideh Hajighasemi ◽  
...  

Atherosclerosis is a chronic, inflammatory disease that mainly affects the arterial intima. The disease is more prevalent in middle-age and older individuals with one or more cardiovascular risk factors, including dyslipidemia, hypertension, diabetes, smoking, obesity, and others. The beginning and development of atherosclerosis has been associated with several immune components, including infiltration of inflammatory cells, monocyte/macrophage-derived foam cells, and inflammatory cytokines and chemokines. Mesenchymal stem cells (MSCs) originate from several tissue sources of the body and have self-renewal and multipotent differentiation characteristics. They also have immunomodulatory and anti-inflammatory properties. Recently, it was shown that MSCs have a regulatory role in plasma lipid levels. In addition, MSCs have shown to have promising potential in terms of treatment strategies for several diseases, including those with an inflammatory component. In this regard, transplantation of MSCs to patients with atherosclerosis has been proposed as a novel strategy in the treatment of this disease. In this review, we summarize the current advancements regarding MSCs for the treatment of atherosclerosis.


2021 ◽  
Author(s):  
Wenya Wang ◽  
Xiao Li ◽  
Chaochu Cui ◽  
Dongling Liu ◽  
Guotian Yin ◽  
...  

Abstract BackgroundAngiogenesis is a key prerequisite for wound healing. The conditioned medium following culture of umbilical cord mesenchymal stem cells (UCMSCs) has a potential to promote angiogenesis, but the efficacy is very low. Autophagy is an important process in protein recycling and a contributor for cell exocrine, which maybe stimulate the release of cytokines from UCMSCs to the medium and enhance the pro-angiogenic efficacy of the conditioned medium.MethodsAutophagy in UCMSCs was induced by 100 nM, 1 µM and 10 µM rapamycin for 6-hour and then detected by LC-3 immunofluorescence staining. After induction, the cells were washed with PBS for 3 times and cultured in fresh medium without rapamycin for additional 24-hour. And then, the conditioned medium was collected for the following experiments. The angiogenic effects of different groups of conditioned medium were verified by in vitro and in vivo tube formation assays in the matrigel-coated plates and matrigel plaques injected in mouse inguinal areas. Finally, the expressions of angiogenic factors including VEGF, FGF-1, FGF-2, TGF-α, MMP-3, MMP-9, PDGF-α, PDGF-β, HIF-1α and Ang II in the autophagic and control UCMSCs were measured by q-PCR assay.ResultsRapamycin induced autophagy of UCMSCs in a dose dependent manner, but the conditioned medium in 100 nM rapamycin-induced group was with the best pro-angiogenic efficacy. Thus, this group of medium was viewed as the optimal conditioned medium. The in vivo tube formation assay showed that angiogenesis in matrigel plaques injected daily with the optimal conditioned medium was more obvious than that injected with the control conditioned medium. Further, the expressions of VEGF, FGF-2, PDGF-α, MMP-9 and HIF-1α were markedly increased in UCMSCs following treatment with 100 nM rapamycin.ConclusionAppropriate autophagy improves the pro-angiogenic efficacy of the conditioned medium, which might be utilized to optimize the applications of UCMSCs-derived conditioned medium in wound healing and tissue repair.Trial registrationNot applicable.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Kiran Shah ◽  
Ashley G. Zhao ◽  
Huseyin Sumer

Osteoarthritis is one of the most common chronic health problems in the world that causes disability and chronic pain with reduced mobility and is a progressive degenerative disease in weight-bearing joints such as the knee. The pathology of the joint resulting from OA includes loss of cartilage volume and cartilage lesions leading to inflammation of the articular joint structures; its incidence and progression are associated with a variety of risk factors. Most of the current treatments focus on symptom management such as physical and occupational therapies, pharmacological intervention for pain management, and surgical intervention with limited success and do not address nor halt the progression of the disease. In this review, we will describe the current treatment options for OA and the exciting new translational medical research currently underway utilising mesenchymal stem cells for OA therapy.


2020 ◽  
Vol 15 (7) ◽  
pp. 623-638
Author(s):  
Saeideh Gholamzadeh Khoei ◽  
Fateme Karimi Dermani ◽  
Sara Malih ◽  
Nashmin Fayazi ◽  
Mohsen Sheykhhasan

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.


2021 ◽  
Vol 14 (3) ◽  
pp. 251 ◽  
Author(s):  
Eun Ha Kang ◽  
Yeong Wook Song

Among the diverse forms of lung involvement, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are two important conditions in patients with rheumatic diseases that are associated with significant morbidity and mortality. The management of ILD and PAH is challenging because the current treatment often provides only limited patient survival benefits. Such challenges derive from their common pathogenic mechanisms, where not only the inflammatory processes of immune cells but also the fibrotic and proliferative processes of nonimmune cells play critical roles in disease progression, making immunosuppressive therapy less effective. Recently, updated treatment strategies adopting targeted agents have been introduced with promising results in clinical trials for ILD ad PAH. This review discusses the epidemiologic features of ILD and PAH among patients with rheumatic diseases (rheumatoid arthritis, myositis, and systemic sclerosis) and the state-of-the-art treatment options, focusing on targeted agents including biologics, antifibrotic agents, and vasodilatory drugs.


2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.


2013 ◽  
Vol 7 (1) ◽  
pp. 275-281 ◽  
Author(s):  
Steven Elder ◽  
Anuhya Gottipati ◽  
Hilary Zelenka ◽  
Joel Bumgardner

Symptomatic osteochondral lesions occur frequently, but relatively few treatment options are currently available. The purpose of this study was to conduct a preliminary investigation into a new tissue engineering approach to osteochondral regeneration. The concept is a biphasic construct consisting of a porous, osteoconductive chitosan-calcium phosphate scaffold supporting a layer of neocartilage formed by marrow-derived mesenchymal stem cells. Two experiments were conducted to assess the feasibility of this approach. The first experiment characterized the attachment efficiency and proliferation of primary human marrow-derived mesenchymal stem cells seeded relatively sparely onto the scaffold’s surface. The second experiment compared two different methods of creating a biphasic construct using a much higher density of primary porcine marrow stromal cells. About 40% of the sparsely seeded human cells attached and proliferated rapidly. Constructs formed by one of the two experimental techniques exhibited a layer of cartilaginous tissue which only partially covered the scaffold’s surface due to inadequate adhesion between the cells and the scaffold. This study demonstrates some potential for the approach to yield an implantable biphasic construct, but further development is required to improve cell-scaffold adhesion.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Man Amanat ◽  
Anahita Majmaa ◽  
Morteza Zarrabi ◽  
Masoumeh Nouri ◽  
Masood Ghahvechi Akbari ◽  
...  

Abstract Background This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. Methods Participants (4–14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). Results There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen’s d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen’s d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (−1.0; 95%CI −1.31, −0.69) and control (β −0.72; 95%CI −1.18, −0.26; Cohen’s d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST −0.035 × 10-3; 95%CI −0.04 × 10-3, −0.02 × 10-3. PTR −0.045 × 10-3; 95%CI −0.05 × 10-3, −0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. Conclusions The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. Trial registration The study was registered with ClinicalTrials.gov (NCT03795974).


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yinzhong Ma ◽  
Lisha Wang ◽  
Shilun Yang ◽  
Dongyu Liu ◽  
Yi Zeng ◽  
...  

Abstract Background The therapeutic efficacy of mesenchymal stem cells (MSCs) of different tissue origins on metabolic disorders can be varied in many ways but remains poorly defined. Here we report a comprehensive comparison of human MSCs derived from umbilical cord Wharton’s jelly (UC-MSCs), dental pulp (PU-MSCs), and adipose tissue (AD-MSCs) on the treatment of glucose and lipid metabolic disorders in type II diabetic mice. Methods Fourteen-to-fifteen-week-old male C57BL/6 db/db mice were intravenously administered with human UC-MSCs, PU-MSCs, and AD-MSCs at various doses or vehicle control once every 2 weeks for 6 weeks. Metformin (MET) was given orally to animals in a separate group once a day at weeks 4 to 6 as a positive control. Body weight, blood glucose, and insulin levels were measured every week. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed every 2 weeks. All the animals were sacrificed at week 6 and the blood and liver tissues were collected for biochemical and histological examinations. Results UC-MSCs showed the strongest efficacy in reducing fasting glucose levels, increasing fasting insulin levels, and improving GTT and ITT in a dose-dependent manner, whereas PU-MSCs showed an intermediate efficacy and AD-MSCs showed the least efficacy on these parameters. Moreover, UC-MSCs also reduced the serum low-density lipoprotein cholesterol (LDL-C) levels with the most prominent potency and AD-MSCs had only very weak effect on LDL-C. In contrast, AD-MSCs substantially reduced the lipid content and histological lesion of liver and accompanying biomarkers of liver injury such as serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, whereas UC-MSCs and PU-MSCs displayed no or modest effects on these parameters, respectively. Conclusions Taken together, our results demonstrated that MSCs of different tissue origins can confer substantially different therapeutic efficacy in ameliorating glucose and lipid metabolic disorders in type II diabetes. MSCs with different therapeutic characteristics could be selected according to the purpose of the treatment in the future clinical practice.


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