scholarly journals Sertoli Cells Possess Immunomodulatory Properties and the Ability of Mitochondrial Transfer Similar to Mesenchymal Stem Cells

Author(s):  
Bianka Porubska ◽  
Daniel Vasek ◽  
Veronika Somova ◽  
Michaela Hajkova ◽  
Michaela Hlaviznova ◽  
...  

Abstract It is becoming increasingly evident that selecting an optimal source of mesenchymal stem cells (MSCs) is crucial for the successful outcome of MSC-based therapies. During the search for cells with potent regenerative properties, Sertoli cells (SCs) have been proven to modulate immune response in both in vitro and in vivo models. Based on morphological properties and expression of surface markers, it has been suggested that SCs could be a kind of MSCs, however, this hypothesis has not been fully confirmed. Therefore, we compared several parameters of MSCs and SCs, with the aim to evaluate the therapeutic potential of SCs in regenerative medicine. We showed that SCs successfully underwent osteogenic, chondrogenic and adipogenic differentiation and determined the expression profile of canonical MSC markers on the SC surface. Besides, SCs rescued T helper (Th) cells from undergoing apoptosis, promoted the anti-inflammatory phenotype of these cells, but did not regulate Th cell proliferation. MSCs impaired the Th17-mediated response; on the other hand, SCs suppressed the inflammatory polarisation in general. SCs induced M2 macrophage polarisation more effectively than MSCs. For the first time, we demonstrated here the ability of SCs to transfer mitochondria to immune cells. Our results indicate that SCs are a type of MSCs and modulate the reactivity of the immune system. Therefore, we suggest that SCs are promising candidates for application in regenerative medicine due to their anti-inflammatory and protective effects, especially in the therapies for diseases associated with testicular tissue inflammation.

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3410
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Inho Choi ◽  
Min Kim ◽  
Jung-Suk Sung

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lijun Chen ◽  
Jingjing Qu ◽  
Quanhui Mei ◽  
Xin Chen ◽  
Yangxin Fang ◽  
...  

AbstractMenstrual blood-derived mesenchymal stem cells (MenSCs) have great potential in regenerative medicine. MenSC has received increasing attention owing to its impressive therapeutic effects in both preclinical and clinical trials. However, the study of MenSC-derived small extracellular vesicles (EVs) is still in its initial stages, in contrast to some common MSC sources (e.g., bone marrow, umbilical cord, and adipose tissue). We describe the basic characteristics and biological functions of MenSC-derived small EVs. We also demonstrate the therapeutic potential of small EVs in fulminant hepatic failure, myocardial infarction, pulmonary fibrosis, prostate cancer, cutaneous wound, type-1 diabetes mellitus, aged fertility, and potential diseases. Subsequently, novel hotspots with respect to MenSC EV-based therapy are proposed to overcome current challenges. While complexities regarding the therapeutic potential of MenSC EVs continue to be unraveled, advances are rapidly emerging in both basic science and clinical medicine. MenSC EV-based treatment has great potential for treating a series of diseases as a novel therapeutic strategy in regenerative medicine.


Author(s):  
Ahmed Elhussieny ◽  
Ken’ichiro Nogami ◽  
Fusako Sakai-Takemura ◽  
Yusuke Maruyama ◽  
AbdElraouf Omar Abdelbakey ◽  
...  

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from both foetal and adult tissues. Several groups demonstrated that transplantation of MSCs promoted the regeneration of skeletal muscle and ameliorated muscular dystrophy in animal models. Mesenchymal stem cells in skeletal muscle, also known as fibro-adipogenic progenitors (FAPs), are essential for the maintenance of skeletal muscle. Importantly, they contribute to fibrosis and fat accumulation in dystrophic muscle. Therefore, MSCs in muscle are a pharmacological target for the treatment of muscular dystrophies. In this chapter, we briefly update the knowledge on mesenchymal stem/progenitor cells and discuss their therapeutic potential as a regenerative medicine treatment of Duchenne muscular dystrophy.


2019 ◽  
Vol 9 (4) ◽  
pp. 627 ◽  
Author(s):  
Hao-Wei Han ◽  
Shigetaka Asano ◽  
Shan-hui Hsu

Intrinsic cellular properties of several types of cells are dramatically altered as the culture condition shifts from two-dimensional (2D) to three-dimensional (3D) environment. Currently, several lines of evidence have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) in regenerative medicine. MSCs not only replenish the lost cells, they also promote the regeneration of impaired tissues by modulating the immune responses. Following the development of 3D cell culture, the enhanced therapeutic efficacy of spheroid-forming MSCs have been identified in several animal disease models by promoting differentiation or trophic factor secretion, as compared to planar-cultured MSCs. Due to the complicated and multifunctional applications in the medical field, MSCs are recently named as medicinal signaling cells. In this review, we summarize the predominant differences of cell–environment interactions for the MSC spheroids formed by chitosan-based substrates and other scaffold-free approaches. Furthermore, several important physical and chemical factors affecting cell behaviors in the cell spheroids are discussed. Currently, the understanding of MSCs spheroid interactions is continuously expanding. Overall, this article aims to review the broad advantages and perspectives of MSC spheroids in regenerative medicine and in future healthcare.


2020 ◽  
Vol 2 (1) ◽  
pp. e25-e30
Author(s):  
Hassan Mubark

Rotator cuff tear (RCT) is primarily a disease of middle-aged and older patients. Observational data estimated linear increment in the frequency of RCT over time due to the degenerative process. However, a good proportion of tears in older patients are asymptomatic and do not require any intervention. Sport and non-sport Injuries can contribute to RCTs. Many RCTs can be treated non-surgically with anti-inflammatory medication, steroid injections, and physical therapy for symptomatic relief and to restore shoulder strength and function. Rotator cuff tendon tears have limited ability to heal on their own and most often surgical repair is recommended in people failing non-operative therapy. The recovery time after surgery can be a lengthy process. There are no conclusive data to support the routine use of biologic therapy like mesenchymal stem cells (MSCs) or platelet-rich plasma (PRP) in the treatment of symptomatic RCTs. Herein we report a full-thickness supraspinatus tear (SST) in an elderly patient’s shoulder following three injuries. The tear was confirmed by ultrasound scan (USS) and magnetic resonance imaging (MRI) with SST of 9 mm in length and 13 mm in width which was unresponsive to anti-inflammatory medicines, rehabilitation and steroid injections. The subject, however, did have a definitive clinical and radiological response to a single therapeutic injection using autologous adipose tissue-derived MSCs combined with PRP, the injections were performed by ultrasound guidance into the subacromial bursa, supraspinatus tendon and tendon insertion respectively. After five months an USS showed some healing of the SST. Eight months post-MSC therapy the subject had significant improvement in symptoms, and dramatic improvement of the Disability of the Arm, Shoulder and Hand (DASH) score from baseline of 88.3 prior to the therapy to 16.3 at the final visit. Follow-up MRI scan revealed complete healing of the SST indicating the possible successful outcome of MSC therapy as an alternative non-surgical treatment.


2021 ◽  
Author(s):  
Seyed Jalil Masoumi ◽  
Negar Hassanshahi ◽  
Seyed-Mohammad Kazem Hosseini-Asl ◽  
Davood Mehrabani ◽  
Seyedeh-Sara Hashemi ◽  
...  

Abstract Complete treatment of ulcerative colitis (UC) is still difficult, while conventional therapies have various adverse effects. Mesenchymal stem cells (MSCs) have anti-inflammatory and immunomodulatory properties to be a therapeutic candidate for UC. We evaluated therapeutic potential of adipose tissue-derived mesenchymal stem cells (AdSCs) in treatment of an acute colitis rat model using histological and molecular assessments. Thirty male Sprague Dawley acetic acid-induced (2 mL of 3%) acute colitis rat models were randomly divided into three equal groups of control receiving 0.5 mL/kg of normal saline, sulfasalazine group receiving 500 mg/kg sulfasalazine and AdSCs group transplanted transrectally with 2×106 MSCs. They were evaluated histologically and by real time PCR for expression of apoptotic genes until 21 days. MSCs were spindle shape and positive for osteogenic and adipogenic differentiation. They displayed mesenchymal and lacked hematopoietic markers. In control group, severe inflammation, edema, ulcer, necrosis and infiltration of leukocytes were noticed. In sulfasalazine group, a moderate inflammation, edema, ulcer, necrosis and infiltration of leukocytes were visible; and in AdSCs group, mild inflammation, congestion, and infiltration of leukocytes were observed with a mild edema, but necrosis was absent in colonic tissue. A stronger decrease in expression of Bax, together with a higher increase in Bcl-2 was noted in AdSCs group. Based on histological and molecular findings, AdSCs were effective to ameliorate colitis lesions through their anti-inflammatory and anti-apoptotic activities showing that transplantation of AdSCS can be a potentially useful strategy in treatment of colitis.


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Devang M. Patel ◽  
Jainy Shah ◽  
Anand S. Srivastava

Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expandedin vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.


2021 ◽  
Vol 91 ◽  
pp. 107266
Author(s):  
Yanwei Li ◽  
Qiuju Sheng ◽  
Chong Zhang ◽  
Chao Han ◽  
Hai Bai ◽  
...  

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