scholarly journals Stem Cells for Augmenting Tendon Repair

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lawrence V. Gulotta ◽  
Salma Chaudhury ◽  
Daniel Wiznia
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Adhesion Formation ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Scar Tissue ◽  
Mechanical Stimuli ◽  
Injury Site ◽  
Attractive Option

Tendon healing is fraught with complications such as reruptures and adhesion formation due to the formation of scar tissue at the injury site as opposed to the regeneration of native tissue. Stem cells are an attractive option in developing cell-based therapies to improve tendon healing. However, several questions remain to be answered before stem cells can be used clinically. Specifically, the type of stem cell, the amount of cells, and the proper combination of growth factors or mechanical stimuli to induce differentiation all remain to be seen. This paper outlines the current literature on the use of stem cells for tendon augmentation.

Bone Marrow Derived Mesenchymal Stem Cell Augmentation of Rabbit Flexor Tendon Healing

Hand Surgery ◽  
2015 ◽  
Vol 20 (03) ◽  
pp. 421-429 ◽  
Author(s):  
Min He ◽  
Aaron Wei Tat Gan ◽  
Aymeric Yu Tang Lim ◽  
James Cho Hong Goh ◽  
James Hoi Po Hui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Flexor Tendon ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Control Group ◽  
High Dose ◽  
Positive Staining ◽  
Flexor Tendon Repair

Background: This study investigated the effect of mesenchymal stem cell implantation on flexor tendon healing using a rabbit model of flexor tendon repair. Specifically, we compared the difference between autologous and allogeneic stem cells. The influence of cell number on the outcome of flexor tendon healing was also investigated. Methods: Repaired tendons on the rear paws of rabbits were randomly assigned into four groups: control group, 1 million autologous cells, 1 million allogeneic cells, and 4 million allogeneic cells. Rabbits were sacrificed at 3 or 8 weeks after surgery. Results: Implantation of 4 million stem cells resulted in a significant increase in range of motion compared with control group at three weeks after surgery. The positive staining of collagen I in healing tendons was enhanced in stem cell treated groups three weeks after surgery. However, stem cells did not improve biomechanical properties of flexor tendons. Conclusions: High dose stem cells attenuated adhesions in the early time point following flexor tendon repair. Further work is needed determine the value of stem cell therapy in flexor tendon healing in humans.

scholarly journals Optimizing growth factor induction of tenogenesis in three-dimensional culture of mesenchymal stem cells

2019 ◽  
Vol 10 ◽  
pp. 204173141984877 ◽  
Author(s):  
Ibtesam Rajpar ◽  
Jennifer G Barrett
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Tendon Healing ◽  
Collagen Type I ◽  
Marker Genes ◽  
Type I ◽  
Cell Alignment ◽  
Tgf Β1

Adult tissue stem cells have shown promise for the treatment of debilitating tendon injuries. However, few comparisons of stem cells from different tissue sources have been made to determine the optimum stem cell source for treating tendon. Moreover, it is likely that the application of tenogenic growth factors will improve tendon stem cell treatments further, and a comprehensive comparison of a number of growth factors is needed. Thus far, different types of stem cells cannot be evaluated in a high-throughput manner. To this end, we have developed an approach to culture mesenchymal stem cells isolated from bone marrow in collagen type I hydrogels with tenogenic growth factors using economical, commercially available supplies. To optimize growth factors for this assay, FGF-2, TGF-β1, IGF-1, and/or BMP-12 were tested singly and in novel combinations of (1) BMP-12 and IGF-1, (2) TGF-β1 and IGF-1, and/or (3) BMP-12 and FGF-2 over 10 days. Our data suggest that BMP-12 supplementation alone results in the strongest expression of tendon marker genes, controlled contractility of constructs, a higher degree of cell alignment, and tendon-like tissue morphology. This easy-to-use benchtop assay can be used to screen novel sources of stem cells and cell lines for tissue engineering and tendon healing applications.

scholarly journals Combating Osteoarthritis through Stem Cell Therapies by Rejuvenating Cartilage: A Review

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Navneet Kumar Dubey ◽  
Viraj Krishna Mishra ◽  
Rajni Dubey ◽  
Shabbir Syed-Abdul ◽  
Joseph R. Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Articular Cartilage ◽  
Current Status ◽  
Self Healing ◽  
Mechanical Stimuli ◽  
Stem Cell Therapies ◽  
Differentiation Potential ◽  
Cell Therapies

Knee osteoarthritis (OA) is a chronic degenerative disorder which could be distinguished by erosion of articular cartilage, pain, stiffness, and crepitus. Not only aging-associated alterations but also the metabolic factors such as hyperglycemia, dyslipidemia, and obesity affect articular tissues and may initiate or exacerbate the OA. The poor self-healing ability of articular cartilage due to limited regeneration in chondrocytes further adversely affects the osteoarthritic microenvironment. Traditional and current surgical treatment procedures for OA are limited and incapable to reverse the damage of articular cartilage. To overcome these limitations, cell-based therapies are currently being employed to repair and regenerate the structure and function of articular tissues. These therapies not only depend upon source and type of stem cells but also on environmental conditions, growth factors, and chemical and mechanical stimuli. Recently, the pluripotent and various multipotent mesenchymal stem cells have been employed for OA therapy, due to their differentiation potential towards chondrogenic lineage. Additionally, the stem cells have also been supplemented with growth factors to achieve higher healing response in osteoarthritic cartilage. In this review, we summarized the current status of stem cell therapies in OA pathophysiology and also highlighted the potential areas of further research needed in regenerative medicine.

Effect of Mechanical Stimulation on the Biomechanics of Stem Cell: Collagen Sponge Constructs for Patellar Tendon Repair

2007 ◽  
Author(s):  
Natalia Juncosa-Melvin ◽  
Jason T. Shearn ◽  
Marc T. Galloway ◽  
Gregory P. Boivin ◽  
Cynthia Gooch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Rotator Cuff ◽  
Mechanical Stimulation ◽  
Soft Tissues ◽  
Tendon Repair ◽  
Collagen Sponge ◽  
Clinical Use ◽  
Attractive Option

Tendons (rotator cuff, Achilles and patellar tendons) are among the most commonly injured soft tissues [1]. Many techniques for repair/reconstruction have been attempted (e.g. sutures, resorbable biomaterials, autografts, and allografts) with varying success. A tissue engineered repair using mesenchymal stem cells (MSCs) is and attractive option [2–4] but the stiffness and strength of currently available constructs are insufficient for clinical use [6].

scholarly journals Hard Dental Tissues Regeneration—Approaches and Challenges

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2558
Author(s):  
Mihaela Olaru ◽  
Liliana Sachelarie ◽  
Gabriela Calin
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Present Review ◽  
Modern Concept ◽  
Dental Tissues ◽  
Tissue Engineering Approach ◽  
Hard Dental Tissues ◽  
Review Reports

With the development of the modern concept of tissue engineering approach and the discovery of the potential of stem cells in dentistry, the regeneration of hard dental tissues has become a reality and a priority of modern dentistry. The present review reports the recent advances on stem-cell based regeneration strategies for hard dental tissues and analyze the feasibility of stem cells and of growth factors in scaffolds-based or scaffold-free approaches in inducing the regeneration of either the whole tooth or only of its component structures.

scholarly journals TGIF1 Gene Silencing in Tendon-Derived Stem Cells Improves the Tendon-to-Bone Insertion Site Regeneration

2015 ◽  
Vol 37 (6) ◽  
pp. 2101-2114 ◽  
Author(s):  
Liyang Chen ◽  
Chaoyin Jiang ◽  
Shashi Ranjan Tiwari ◽  
Amrit Shrestha ◽  
Pengcheng Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Silencing ◽  
Healing Process ◽  
Insertion Site ◽  
Tendon Repair ◽  
Scar Tissue ◽  
Connective Tissues ◽  
Expression Rate ◽  
Low Levels ◽  
Derivatives Of

Background/Aims: The slow healing process of tendon-to-bone junctions can be accelerated via implanted tendon-derived stem cells (TDSCs) with silenced transforming growth interacting factor 1 (TGIF1) gene. Tendon-to-bone insertion site is the special form of connective tissues derivatives of common connective progenitors, where TGF-β plays bidirectional effects (chondrogenic or fibrogenic) through different signaling pathways at different stages. A recent study revealed that TGF-β directly induces the chondrogenic gene Sox9. However, TGIF1 represses the expression of the cartilage master Sox9 gene and changes its expression rate against the fibrogenesis gene Scleraxis (Scx). Methods: TGIF1 siRNA was transduced or TGIF1 was over-expressed in tendon-derived stem cells. Following suprapinatus tendon repair, rats were either treated with transduced TDSCs or nontransduced TDSCs. Histologic examination and Western blot were performed in both groups. Results: In this study, the silencing of TGIF1 significantly upregulated the chondrogenic genes and markers. Similarly, TGIF1 inhibited TDSC differentiation into cartilage via interactions with TGF-β-activated Smad2 and suppressed the phosphorylation of Smad2. The area of fibrocartilage at the tendon-bone interface was significantly increased in the TGIF1 (-) group compared with the control and TGIF1-overexpressing groups in the early stages of the animal model. The interface between the tendon and bone showed a increase of new bone and fibrocartilage in the TGIF1 (-) group at 4 weeks. Fibrovascular scar tissue was observed in the TGIF1-overexpressing group and the fibrin glue only group. Low levels of fibrocartilage and fibrovascular scar tissue were found in the TDSCs group. Conclusion: Collectively, this study shows that the tendon-derived stem cell modified with TGIF1 gene silencing has promising effects on tendon-to-bone healing which can be further explored as a therapeutic tool in regenerative medicine.

scholarly journals Understanding the Influence of Substrate When Growing Tumorspheres

2020 ◽  
Author(s):  
Lucía Benítez ◽  
Lucas Barberis ◽  
Luciano Vellón ◽  
Carlos Alberto Condat
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Stem Cell Niche ◽  
Cell Number ◽  
Hard Substrate ◽  
Cell Niche

Abstract Background: Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods: A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results: The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions: Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. A specific condition for the growth of the cancer stem cell number is also obtained.

Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 312-317 ◽  
Author(s):  
Estelle J. K. Noach ◽  
Albertina Ausema ◽  
Jan H. Dillingh ◽  
Bert Dontje ◽  
Ellen Weersing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factors ◽  
Low Dose ◽  
Donor Cell ◽  
Hematopoietic Growth Factors ◽  
Cell Engraftment ◽  
Total Body

Abstract Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.

A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

2021 ◽  
Author(s):  
Ganesan Jothimani ◽  
Surajait Pathak ◽  
Suman Dutta ◽  
Asim K. Duttaroy ◽  
Antara Banerjee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Expression Patterns ◽  
Functional Enrichment ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Anti Cancer

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.

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