scholarly journals Adipose-derived stem cell exosomes facilitate rotator cuff repair by mediating tendon-derived stem cells

2021 ◽  
Vol 16 (4) ◽  
pp. 359-372
Author(s):  
Guojian Fu ◽  
Liangyu Lu ◽  
Zhangyi Pan ◽  
Aoyuan Fan ◽  
Feng Yin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rotator Cuff ◽  
Rotator Cuff Repair ◽  
Injury Model ◽  
And Migration ◽  
Adipose Derived Stem Cell ◽  
Cuff Repair

Aim: To evaluate the potential capability of adipose-derived stem cell exosomes (ADSC-exos) on rotator cuff repair by mediating the tendon-derived stem cells (TDSCs) and explored the mechanism. Methods: First, we investigated the growth, survival and migration of TDSCs in the presence of ADSC-exos in vitro. Using a rat rotator cuff injury model to analyze the ability of the ADSC-exos to promote rotator cuff healing in vivo. Results: The hydrogel with ADSC-exos significantly improved the osteogenic and adipogenesis differentiation and enhanced the expression of RUNX2, Sox-9, TNMD, TNC and Scx and the mechanical properties of the articular portion. Conclusion: The ADSC-exos have the potential to promote the rotator cuff repair by mediating the TDSCs.

scholarly journals Stem cell application in rotator cuff repair: Interposition stem cell sheet versus overlaid stem cell sheet

2020 ◽  
Author(s):  
Jae hee Choi ◽  
Michael Seungcheol Kang ◽  
Myung Jin Shin ◽  
Dong Min Kim ◽  
Yu Na Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rotator Cuff ◽  
Rotator Cuff Repair ◽  
Surgical Repair ◽  
Cell Sheet ◽  
Biomechanical Analysis ◽  
Control Group ◽  
Cell Sheets ◽  
Cuff Repair

Abstract Background Stem cells are an effective method of biologic healing and can be used to enhance the natural enthesis of the tendon-to-bone junction in rotator cuff repair. The purpose of this study was to investigate if the application of engineered stem cell sheets using adipose-derived cells (ADSCs) was effective in regeneration of natural enthesis and if there was a difference in the result of repair depending on the applied location Methods A chronic rotator cuff tear model was induced for 2 weeks, and cell sheets made using ADSCs isolated from rats were transplanted into the tendon-to-bone junction during surgical repair. Depending on the transplant location of the cell sheet, the difference in rotator cuff healing level between the overlaid group and the interposition group was compared to the surgical repair only group. The samples were obtained based on the tendon-to-bone junction and analysis of gross morphology, histology staining, and biomechanical analysis were performed. Results The differentiation potentials of ADSCs as stem cells were confirmed, as was the potential for tenogenic differentiation by growth factors. ADSCs were prepared as a sheet form to maintain the shape at the target site and to be easily attached. GFP-expressing ADSCs were proliferated in vivo and observed at the transplantation site. The overall healing level was better in the cell sheet transplanted group than in the control group that surgical repair only. Additionally, differences in healing level were shown depending on the cell sheet location by morphological, histological, and biomechanical perspectives. Histological results showed that the interposition transplantation group (1.75 ± 0.43, P = 0.004) showed better fibrocartilage formation and collagen orientation at the junction than the overlaid transplantation group (0.86 ± 0.83). Conclusion In the chronic rotator cuff repair model, the engineered stem cell sheets enhanced the regeneration of the tendon-to-bone junction. This regeneration was more effective when the stem cell sheet was interpositioned at the tendon-to-bone interface. Trial registration: Not applicable

scholarly journals Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Manuel Pedro Jimenez-García ◽  
Antonio Lucena-Cacace ◽  
Daniel Otero-Albiol ◽  
Amancio Carnero
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Neural Crest ◽  
Tumor Suppressors ◽  
Homeobox Genes ◽  
Neuronal Cell ◽  
Cell Gene Expression

AbstractThe EMX (Empty Spiracles Homeobox) genes EMX1 and EMX2 are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. The EMX1 and EMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed that EMX1/EMX2 act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4, SOX2, KLF4, MYC, NANOG, NES, and PROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lacking Emx genes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression and nestin expression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

Evaluation of BioCorkscrew and Bioknotless RC suture anchor rotator cuff repair fixation: an in vitro biomechanical study

2007 ◽  
Vol 15 (11) ◽  
pp. 1375-1381 ◽  
Author(s):  
Jennifer Tucker Ammon ◽  
John Nyland ◽  
Haw Chong Chang ◽  
Robert Burden ◽  
David N. M. Caborn
Keyword(s):  
Rotator Cuff ◽  
Rotator Cuff Repair ◽  
Suture Anchor ◽  
Biomechanical Study ◽  
Cuff Repair

Elimination of Reperfusion-Induced Microcirculatory Alterations In Vivo by Adipose-Derived Stem Cell Supernatant without Adipose-Derived Stem Cells

2015 ◽  
Vol 135 (4) ◽  
pp. 1056-1064 ◽  
Author(s):  
Wei Z. Wang ◽  
Xin-Hua Fang ◽  
Shelley J. Williams ◽  
Linda L. Stephenson ◽  
Richard C. Baynosa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adipose Derived Stem Cells ◽  
Adipose Derived Stem Cell ◽  
Cell Supernatant

scholarly journals TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model

2016 ◽  
Vol 38 (1) ◽  
pp. 319-329 ◽  
Author(s):  
Yulei Gao ◽  
Yinquan Zhang ◽  
Yanghu Lu ◽  
Yi Wang ◽  
Xingrui Kou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Bone Healing ◽  
Rotator Cuff Repair ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Cuff Repair

Background/Aims: This study investigated the effect of silencing TOB1 (Transducer of ERBB2, 1) expression in bone marrow-derived mesenchymal stem cells (MSCs) on MSC-facilitated tendon-bone healing in a rat supraspinatus repair model. Methods: Rat MSCs were transduced with a recombinant lentivirus encoding short hairpin RNA (shRNA) against TOB1. MSC cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The effect of MSCs with TOB1 deficiency on tendon-bone healing in a rat rotator cuff repair model was evaluated by biomechanical testing, histological analysis and collagen type I and II gene expression. An upstream regulator (miR-218) of TOB1 was determined in MSCs. Results: We found that knockdown of TOB1 significantly increased the proliferative activity of rat MSCs in vitro. When MSCs with TOB1 deficiency were injected into injured rat supraspinatus tendon-bone junctions, the effect on tendon-bone healing was enhanced compared to treatment with control MSCs with normal TOB1 expression, as evidenced by elevated levels of ultimate load to failure and stiffness, increased amount of fibrocartilage and augmented expression of collagen type I and type II genes. In addition, we found that the TOB1 3′ untranslated region is a direct target of miR-218. Similar to the effect of TOB1 deficiency, overexpression of miR-218 effectively promoted tendon-bone healing in rat. Conclusion: These results suggest that TOB1 may play a negative role in the effect of MSCs on tendon-bone healing, and imply that expression of TOB1 may be regulated by miR-218.

scholarly journals Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

The Role of the Renin–Angiotensin System in the Cancer Stem Cell Niche

2021 ◽  
pp. 002215542110262
Author(s):  
Ethan J. Kilmister ◽  
Swee T. Tan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Renin Angiotensin System ◽  
Epidemiological Data ◽  
Malignant Cells ◽  
Angiotensin System ◽  
Renin Angiotensin

Cancer stem cells (CSCs) drive metastasis, treatment resistance, and tumor recurrence. CSCs reside within a niche, an anatomically distinct site within the tumor microenvironment (TME) that consists of malignant and non-malignant cells, including immune cells. The renin–angiotensin system (RAS), a critical regulator of stem cells and key developmental processes, plays a vital role in the TME. Non-malignant cells within the CSC niche and stem cell signaling pathways such as the Wnt, Hedgehog, and Notch pathways influence CSCs. Components of the RAS and cathepsins B and D that constitute bypass loops of the RAS are expressed on CSCs in many cancer types. There is extensive in vitro and in vivo evidence showing that RAS inhibition reduces tumor growth, cell proliferation, invasion, and metastasis. However, there is inconsistent epidemiological data on the effect of RAS inhibitors on cancer incidence and survival outcomes, attributed to different patient characteristics and methodologies used between studies. Further mechanistic studies are warranted to investigate the precise effects of the RAS on CSCs directly and/or the CSC niche. Targeting the RAS, its bypass loops, and convergent signaling pathways participating in the TME and other key stem cell pathways that regulate CSCs may be a novel approach to cancer treatment:

Accept or Reject: The Role of Immune Tolerance in the Development of Stem Cell Therapies and Possible Future Approaches

2020 ◽  
pp. 019262332091824
Author(s):  
Richard Haworth ◽  
Michaela Sharpe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Immune Recognition ◽  
Cell Of Origin ◽  
In Vivo Models ◽  
Cell Product ◽  
A Cell

In 2011, Goldring and colleagues published a review article describing the potential safety issues of novel stem cell-derived treatments. Immunogenicity and immunotoxicity of the administered cell product were considered risks in the light of clinical experience of transplantation. The relative immunogenicity of mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) was being addressed through in vitro and in vivo models. But the question arose as to whether the implanted cells needed to be identical to the recipient in every respect, including epigenetically, to evade immune recognition? If so, this set a high bar which may preclude use of many cells derived from iPSCs which have vestiges of a fetal phenotype and epigenetic memory of their cell of origin. However, for autologous iPSCs, the immunogenicity reduces once the surface antigen expression profile becomes close to that of the parent somatic cells. Therefore, a cell product containing incompletely differentiated cells could be more immunogenic. The properties of the administered cells, the immune privilege of the administration site, and the host immune status influence graft success or failure. In addition, the various approaches available to characterize potential immunogenicity of a cell therapy will be discussed.

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