Blog

• Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo

  Posted in: Stem Cell Treatment Houston | Posted on: 23-Feb-2016

  Abstract

  Objective: Lubricin expression in the superficial cartilage will be a crucial factor in the success of carti-lage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and theuse of aggregates of MSCs has some advantages in terms of chondrogenic potential andefficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elu-cidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricinin vitro chondrogenesis, (2) whether aggregates of human MSCs pro-moted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats.

  Methods: For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteo- chondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages.

  Results: In in vitro analysis, lubricin was detected in the superficial zone of the pellets and condi-tioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pel-lets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis.

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• Long-term effect of Prolotherapy on symptomatic rotator cuff tendinopathy

  Posted in: General | Posted on: 23-Feb-2016

  Abstract

  Introduction: The objective of this study was to assess a long-term clinical effect of Prolotherapy on chronic symptomatic rotator cuff tendinopathy.

  Methods: We conducted a retrospective, uncontrolled study in the outpatient setting with 12 months follow-up. Adults diagnosed clinically and radiologically with rotator cuff tendinopathy that has been persisting for a minimum of six months were included. Patients received 15% extra-articular and 25% intra-articular hyperosmolar dextrose injections, repeated at weeks 5, 9, 13, 17 and 21. Primary outcome measure was validated Shoulder Pain and Disability Index (SPADI). Secondary outcome measure was validated visual pain analogue scale (VAS 0-10). The third outcome measures were patient's satisfaction with Prolotherapy and adverse reactions after injections.

  Results: Twenty-one patients, 14 male and 7 female were treated with 6 sessions of hyperosmolar dextrose Prolotherapy repeated every 4 weeks. Average SPADI before starting the treatment was 73.995

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• Adipose stem cells differentiated chondrocytes regenerate damaged cartilage in rat model of Osteoarthritis

  Posted in: Stem Cell Treatment Houston | Posted on: 22-Feb-2016

  Abstract

  Transplantation of mesenchymal stem cells (MSCs) or autologous chondrocytes has been shown to repair damages to articular cartilage due to osteoarthritis (OA). However survival of transplanted cells is considerably reduced in the osteoarthritic environment and it affects successful outcome of the transplantation of the cells. Differentiated chrondroytes derived from adipose stem cells have been proposed as an alternative source and our study investigated this possibility in rats. We investigated the regenerative potential of ASCs and DCs in osteoarthritic environment in the repair of cartilage in rats. We found that ASCs maintained fibroblast morphology in vitro and also expressed CD90 and CD29. Furthermore, ASCs differentiated into chondrocytes, accompanied by increased level of proteoglycans and expression of chondrocytes specific genes, such as, Acan and Col2a1. Histological examination of transplanted knee joints showed regeneration of cartilage tissue compared to control OA knee joints. Increase in gene expression for Acan, Col2a1 with concomitant decrease in the expression of Col1a1 suggested formation of hyaline like cartilage. A significant increase in differentiation index was observed in DCs and ASCs transplanted knee joints (P = 0.0110 vs P = 0.0429) when compared to that in OA control knee joints. Furthermore, transplanted DCs showed increased proliferation along with reduction in apoptosis as compared to untreated control.

  In conclusion, DCs showed better survival and regeneration potential as compared with ASCs in rat model of OA and thus may serve a better option for regeneration of osteoarthritic cartilage.

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• Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes.

  Posted in: General | Posted on: 21-Feb-2016

  Abstract

  BACKGROUND: Platelet-rich plasma (PRP) has recently been postulated as a treatment for osteoarthritis (OA). Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes.

  HYPOTHESIS: Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes.

  STUDY DESIGN:Controlled laboratory study.

  METHODS: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. Medium was supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1), aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin-endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG) content, nitric oxide (NO) production, and nuclear factor kappa B (NFκB) activation were studied.

  RESULTS: Platelet-rich plasma releasate diminished IL-1 beta-induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced IL-1 beta-induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene expression and GAG content were not influenced by IL-1 beta or additional PRPr. Matrix metalloproteinase 13 gene expression and NO production were upregulated by IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta-induced NFκB activation to control levels containing no IL-1 beta.

  CONCLUSION: Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta-mediated effects on human osteoarthritic chondrocytes, including inhibition of NFκB activation.

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• Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

  Posted in: General | Posted on: 18-Feb-2016

  Abstract

  Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives, such as platelet-rich plasma, have consistently shown to potentiate stem cell proliferation, migration, and differentiation. Here, we review the spectrum of platelet-rich blood derivatives, discuss their current applications in tissue engineering and regenerative medicine, reflect on their effect on stem cells, and highlight current translational challenges.

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• Does platelet-rich plasma have a role in the treatment of osteoarthritis?

  Posted in: General | Posted on: 16-Feb-2016

  Abstract

  Platelet-rich plasma (PRP) has been generating considerable attention as an intra-articular treatment to alleviate the symptoms of osteoarthritis. Activated platelets release a host of soluble mediators such as growth factors and cytokines, thereby inducing complex interactions that vary across tissues within the joint. In vivo, PRP may promote chondrocyte proliferation and differentiation. The available data are somewhat conflicting regarding potential effects on synovial cells and angiogenesis modulation. PRP probably exerts an early anti-inflammatory effect, which may be chiefly mediated by inhibition of the NF-κB pathway, a hypothesis that requires confirmation by proof-of-concept studies. It is far too early to draw conclusions about the efficacy of PRP as a treatment for hip osteoarthritis. The only randomized trial versus hyaluronic acid showed no significant difference in effects, and no placebo-controlled trials are available. Most of the randomized trials in knee osteoarthritis support a slightly greater effect in alleviating the symptoms compared to visco-supplementation, most notably at the early stages of the disease, although only medium-term data are available. Many uncertainties remain, however, regarding the best administration regimen. Serious adverse effects, including infections and allergies, seem rare, although post-injection pain is more common than with other intra-articular treatments for osteoarthritis.

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• Cytokine-release kinetics of platelet-rich plasma according to various activation protocols

  Posted in: General | Posted on: 15-Feb-2016

  Abstract

  Objectives: This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols.

  Methods: Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay.

  Results: The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration.

  Conclusion: The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation.

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• Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration

  Posted in: Stem Cell Treatment Houston | Posted on: 10-Feb-2016

  Abstract

  Purpose: Bone marrow concentrate (BMC) and platelet-rich plasma (PRP) are used extensively in regenerative medicine. The aim of this study was to determine differences in the cellular composition and cytokine concentrations of BMC and PRP and to compare two commercial BMC systems in the same patient cohort.

  Methods: Patients (29) undergoing orthopaedic surgery were enrolled. Bone marrow aspirate (BMA) was processed to generate BMC from two commercial systems (BMC-A and BMC-B). Blood was obtained to make PRP utilizing the same system as BMC-A. Bone marrow-derived samples were cultured to measure colony-forming units, and flow cytometry was performed to assess mesenchymal stem cell (MSC) markers. Cellular concentrations were assessed for all samples. Catabolic cytokines and growth factors important for cartilage repair were measured using multiplex ELISA.

  Results: Colony-forming units were increased in both BMCs compared to BMA (p < 0.0001). Surface markers were consistent with MSCs. Platelet counts were not significantly different between BMC-A and PRP, but there were differences in leucocyte concentrations. TGF-β1 and PDGF were not different between BMC-A and PRP. IL-1ra concentrations were greater (p = 0.0018) in BMC-A samples (13,432 pg/mL) than in PRP (588 pg/mL). The IL-1ra/IL-1β ratio in all BMC samples was above the value reported to inhibit IL-1β.

  Conclusions: The bioactive factors examined in this study have differing clinical effects on musculoskeletal tissue. Differences in the cellular and cytokine composition between PRP and BMC and between BMC systems should be taken into consideration by the clinician when choosing a biologic for therapeutic application.

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• Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial

  Posted in: General | Posted on: 10-Feb-2016

  Abstract

  Background: Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded.

  Purpose: To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA).

  Study Design: Randomized controlled trial; Level of evidence, 1.

  Methods: In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year.

  Results: No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group.

  Conclusion: ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment.

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• CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice

  Posted in: Stem Cell Treatment Houston | Posted on: 09-Feb-2016

  Abstract

  Background: The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146+ and CD146- MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated.

  Methods: Flow cytometry was used to quantify IL-6 and TGF-β1 expressed on CD146+ and CD146- MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA).

  Results: Compared with CD146- MSCs, CD146+ MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146- cells but not when exposed to CD146+ cells both in vitro and in vivo. IA injection of CD146+ MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A+ CD146+ cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression.

  Conclusions: This study suggests that CD146+ cells have greater potency than CD146- cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146+ cells in treating inflammatory arthritis.

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• Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial

  Posted in: General | Posted on: 07-Feb-2016

  Abstract

  Background: Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded.

  Purpose: To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA).

  Study Design: Randomized controlled trial; Level of evidence, 1.

  Methods: In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year.

  Results: No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group.

  Conclusion: ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this treatment.

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• High-concentrate PRP Promotes Healing in Long-Bone Nonunions

  Posted in: General | Posted on: 02-Feb-2016

  A study of patients with nonunited fractures of long bones found that injection of platelet-rich plasma (PRP) enhanced the rate of union, demonstrated by definitive radiographic evidence of healing.

  The study, "Platelet Concentrate in Treatment of Non Union of Long Bones," was conducted by Vijay Kumar, MD; Anjan Trikha, MD; and Rajesh Malhotra, MS, who presented the results. It was conducted at the All India Institute of Medical Sciences in New Delhi, India.

  Patients in the study had clinical and radiological signs of nonunion of the long bones, stable internal fixation or stable reduction with plaster immobilization, and more than 90 percent contact between the fracture fragments. Nonunion was defined as a fracture that had not shown progressive evidence of healing more than 6 months after injury or more than 4 months from last fracture site operation. Patients with gap nonunions, skin infections, or pseudarthrosis; patients unfit for autologous donation (platelet count <130 ×— 109/L, or age older than 60 years); and patients with thrombocytopenia or hypofibrogenemia, or patients taking medicines known to influence platelet function (like aspirin) were excluded from the study.

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• Intra-articular platelet-rich plasma for the treatment of osteoarthritis

  Posted in: General | Posted on: 02-Feb-2016

  Abstract

  Platelet-rich plasma (PRP) is an autologous blood derivative that has been used in different medical fields, ranging from dermatology to ophthalmology and orthopaedic surgery, with the aim of stimulating tissue healing through the local administration of a milieu of platelet-derived growth factors and other bioactive molecules (1). In the orthopaedic practice its main application is in sports medicine (2,3) and in the treatment of degenerative disorders, in particular osteoarthritis (OA) (4). Due to its intrinsic features, PRP is believed to play a beneficial role in joint tissue homeostasis, exerting a positive modulation on all the articular tissues involved in the OA degenerative process, i.e., cartilage, menisci, and synovia (5).

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• Review Article of Corticosteroid Injections Use in Acute and Chronic Lateral Epicondylgia. An Update of the Currently Available Literature

  Posted in: General | Posted on: 01-Feb-2016

  Abstract

  Purpose:The aim of this study is to assess the effectiveness of corticosteroid injections (CSI) in treatment of acute and chronic Lateral Epicondylgia (LE) by summarising all recent updates related to this injection in LE.

  Conclusion:Corticosteroid injections have a long record of use in LE, and are frequently requested by patients. However, this review could present a strong argument against the use of CSI, particularly for chronic LE, since no long term benefits were found. This concurs with other reviews. While CSI have a well-documented short-term benefit, they appear to have a detrimental effect with longer follow up, such as an increase in recurrence rate.

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• Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles

  Posted in: Stem Cell Treatment Houston | Posted on: 26-Jan-2016

  Abstract

  We propose a method of preparing a novel cell carrier derived from natural cartilage extracellular matrix (ECM), designated cartilage ECM -derived particles (CEDPs). Through a series of processes involving pulverization, sieving, and decellularization, fresh cartilage was made into CEDPs with a median diameter of 263 ±48 μm. Under microgravity culture conditions in a rotary cell culture system (RCCS), bone marrow stromal cells (BMSCs) can proliferate rapidly on the surface of CEDPs with high viability. Histological evaluation and gene expression analysis indicated that BMSCs were differentiated into mature chondrocytes after 21 days of culture without the use of exogenous growth factors. Functional cartilage microtissue aggregates of BMSC-laden CEDPs formed as time in culture increased. Further, the microtissue aggregates were directly implanted into trochlear cartilage defects in a rat model (CEDP+MSC group). Gait analysis and histological results indicated that the CEDP+MSC group obtained better and more rapid joint function recovery and superior cartilage repair compared to the control groups, in which defects were treated with CEDPs alone or only fibrin glue, at both 6 and 12 weeks after surgery. In conclusion, the innovative cell carrier derived from cartilage ECM could promote chondrogenic differentiation of BMSCs, and the direct use of functional cartilage microtissue facilitated cartilage regeneration. This strategy for cell culture, stem cell differentiation and one-step surgery using cartilage microtissue for cartilage repair provides novel prospects for cartilage tissue engineering and may have further broad clinical applications.

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• Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair

  Posted in: Stem Cell Treatment Houston | Posted on: 26-Jan-2016

  Abstract

  The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their otentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell (MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.

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• Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair

  Posted in: Stem Cell Treatment Houston | Posted on: 26-Jan-2016

  Abstract

  Introduction: Articular cartilage is renowned for its poor intrinsic capacity for repair. Current treatments for osteoarthritis are limited in their ability to reliably restore the native articular cartilage structure and function. Mesenchymal stem cells (MSCs) present an attractive treatment option for articular cartilage repair, with a recent expansion of clinical trials investigating their use in patients.

  Areas covered: This paper provides a current overview of the clinical evidence on the use of MSCs in articular cartilage repair.

  Expert opinion: The article demonstrates robust clinical evidence that MSCs have significant potential for the regeneration of hyaline articular cartilage in patients. The majority of clinical trials to date have yielded significantly positive results with minimal adverse effects. However the clinical research is still in its infancy. The optimum MSC source, cell concentrations, implantation technique, scaffold, growth factors and rehabilitation protocol for clinical use are yet to be identified. A larger number of randomised control trials are required to objectively compare the clinical efficacy and long-term safety of the various techniques. As the clinical research continues to evolve and address these challenges, it is likely that MSCs may become integrated into routine clinical practice in the near future.

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• Application of marrow mesenchymal stem cell-derived extracellular matrix in peripheral nerve tissue engineering

  Posted in: Stem Cell Treatment Houston | Posted on: 24-Jan-2016

  Abstract

  To advance molecular and cellular therapy into the clinic for peripheral nerve injury, modification of neural scaffolds with the extracellular matrix (ECM) of peripheral nerves has been established as a promising alternative to direct inclusion of support cells and/or growth factors within a neural scaffold, while cell-derived ECM proves to be superior to tissue-derived ECM in the modification of neural scaffolds. Based on the fact that bone marrow mesenchymal stem cells (BMSCs), just like Schwann cells, are adopted as support cells within a neural scaffold, in this study we used BMSCs as parent cells to generate ECM for application in peripheral nerve tissue engineering. A chitosan nerve guidance conduit (NGC) and silk fibroin filamentous fillers were respectively prepared for co-culture with purified BMSCs, followed by decellularization to stimulate ECM deposition. The ECM-modified NGC and lumen fillers were then assembled into a chitosan-silk fibroin-based, BMSC-derived, ECM-modified neural scaffold, which was implanted into rats to bridge a 10 mm-long sciatic nerve gap. Histological and functional assessments after implantation showed that regenerative outcomes achieved by our engineered neural scaffold were better than those achieved by a plain chitosan-silk fibroin scaffold, and suggested the benefits of BMSC-derived ECM for peripheral nerve repair. Copyright

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• The development of submucosal injection of platelet rich plasma for accelerating orthodontic tooth movement and preserving pressure side alve

  Posted in: General | Posted on: 18-Jan-2016

  Abstract

  Although the surgical-assisted accelerated orthodontic tooth movement has been proved to be the most effective one currently, its disadvantages are it is a bone surgery, and it causes loss of alveolar bone that undermines the periodontal support of the target teeth. The submucosal injection of platelet rich plasma (PRP) is a technique developed for accelerating orthodontic tooth movement by simulating the effects of bone insult without surgery and loss of alveolar bone. We have revealed clinically that submucosal injection of PRP accelerated the mandibular or maxillary alignment 1.7 folds faster in average, and the acceleration was dose-dependent when the PRP fold (platelet count in PRP/platelet count in blood) was <12.5. The optimal PRP fold for a more than 2-fold acceleration of orthodontic alignment ranged from 9.5 to 12.5 folds. On the other hand, the injection of PRP on the pressure side of en masse anterior retraction decreased 71-77% of alveolar bone loss, and this was dose-dependent. The pressure side of en masse anterior retraction had no alveolar bone loss when the PRP fold was higher than 11.0. In conclusion, the optimal PRP fold for the best performance in acceleration of orthodontic tooth movement and preservation of the pressure side alveolar bone is 11.0-12.5.

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• Pharmacological priming of adipose-derived stem cells promotes myocardial repair

  Posted in: Stem Cell Treatment Houston | Posted on: 18-Jan-2016

  Abstract

  Adipose-derived stem cells (ADSCs) have myocardial regeneration potential, and transplantation of these cells following myocardial infarction (MI) in animal models leads to modest improvements in cardiac function. We hypothesized that pharmacological priming of pre-transplanted ADSCs would further improve left ventricular functional recovery after MI. We previously identified a compound from a family of 3,5-disubstituted isoxazoles, ISX1, capable of activating an Nkx2-5-driven promoter construct. Here, using ADSCs, we found that ISX1 (20 mM, 4 days) triggered a robust, dose-dependent, fourfold increase in Nkx2-5 expression, an early marker of cardiac myocyte differentiation and increased ADSC viability in vitro. Co-culturing neonatal cardiomyocytes with ISX1-treated ADSCs increased early and late cardiac gene expression. Whereas ISX1 promoted ADSC differentiation toward a cardiogenic lineage, it did not elicit their complete differentiation or their differentiation into mature adipocytes, osteoblasts, or chondrocytes, suggesting that re-programming is cardiomyocyte specific. Cardiac transplantation of ADSCs improved left ventricular functional recovery following MI, a response which was significantly augmented by transplantation of ISX1- pretreated cells. Moreover, ISX1-treated and transplanted ADSCs engrafted and were detectable in the myocardium 3 weeks following MI, albeit at relatively small numbers. ISX1 treatment increased histone acetyltransferase (HAT) activity in ADSCs, which was associated with histone 3 and histone 4 acetylation. Finally, hearts transplanted with ISX1-treated ADSCs manifested significant increases in neovascularization, which may account for the improved cardiac function. These findings suggest that a strategy of drug-facilitated initiation of myocyte differentiation enhances exogenously transplanted ADSC persistence in vivo, and consequent tissue neovascularization, to improve cardiac function.

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