Stem Cell Treatment Houston

  • Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis

    Background:

    Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment.

    Methods: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant.

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  • Stem cells in orthopaedics

    Abstract

    Sharing new ideas and approaches is needed to advance basic scientific research as well as the clinical application of stem cells. In this newsletter we present the current knowledge in stem cell research and therapy within the field of orthopaedics, presenting the definitions, types and sources of the stem cells. The second part of this newsletter focuses on the clinical application of stem cells in the therapy of tissues with very limited capacity for self-regeneration; this includes tendons and ligaments, particularly found in rotator cuff rupture. The sever problems associated with articular cartilage repair have lead to the need for the development of clinical research, with the aim of finding efficient clinical applications of stem cell therapy in cartilage defects and osteoarthritis. However in addition to this, such therapy could be used for the regeneration of bone, as in bone defect repair. The clinical outcome of stem cell therapy is a promising option for the treatment of cartilage, bone and tendon defects; however an increased sample size and additional long-term prospective randomised studies are needed to confirm these preliminary results.

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  • Researchers report good first results using blood stem cells, HA to regenerate cartilage

    Scientific investigators from Malaysia reported the first evidence of hyaline cartilage regeneration using intra-articular injections of autologous peripheral blood stem cells in combination with hyaluronic acid.

    In their clinical trial, researchers from the Kuala Lumpur Sports Medicine Centre and the University Putra Malaysia followed 10 patients with full-thickness chondral defects treated with arthroscopic multiple subchondral drilling. The investigators followed the patients for a minimum of 2 years.

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  • Pluripotent Stem Cells and Skeletal Regeneration —Promise and Potential

    Abstract

    The bone is a regenerative tissue, capable of healing itself after fractures. However, some circumstances such as critical-size defects, malformations, and tumor destruction may exceed the skeleton\'s capacity for self-repair. In addition, bone mass and strength decline with age, leading to an increase in fragility fractures. Therefore, the ability to generate large numbers of patient-specific osteoblasts would have enormous clinical implications for the treatment of skeletal defects and diseases. This review will highlight recent advances in the derivation of pluripotent stem cells, and in their directed differentiation towards bone-forming osteoblasts.

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  • Histological Evaluation of Bone Marrow Derived Stem Cell Therapy on Experimentally Induced Osteoarthritis in Albino Rats\' Knee Joint

    Abstract:

    Aim of work: This work aims to evaluate the efficacy of intra-articular injection of bone marrow derived-mesenchymal stem cells (MSCs) in treatment of mono-iodoacetate (MIA) induced osteoarthritis in rat knee joint monitored by histological and immunohistochemical methods. Material and methods: this study was carried out on 45 adult male albino rats. They were classified into 4 groups: group I (control group), group II (osteoarthritic group) in which rats received 1 mg of MIA and sacrificed after 2 weeks and after 4 weeks, group III (stem cell treated group) in which rats received MSCs 2 weeks after MIA injection or 4 weeks after MIA and sacrificed 2 weeks later and group IV (untreated group) in which rats received PBS 2 weeks after MIA injection or 4 weeks after MIA and sacrificed 2 weeks later. Sections were taken from rats' knee joints and stained with Hematoxylin and Eosin, toluidine blue, immunohistochemichal stains for collagen type II. Sections were examined by light microscopy. The mean articular cartilage (AC) thickness, optical density of cartilage matrix proteoglycan and area percent of collagen type II immunoreactivity were measured using image analyzer and statistically analyzed.

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  • Mesenchymal stem cells reside in anterior cruciate ligament remnants in situ

    Abstract

    Purpose

    It has been reported that the anterior cruciate ligament (ACL) has certain self-healing ability after acute injury or with primary suture repair. Many studies have confirmed that a remnant preservation technique with ACL reconstruction contributes to biological augmentation for ACL healing. However, it remains unclear whether mesenchymal stem cells (MSC) reside in ACL remnants in situ. The aim of this study was to investigate the methods of culture and identification of MSC derived from the remnants of ACL rupture patients and to analyse these MSC\'s properties.

    Methods

    The cells of ACL remnants from the ACL rupture patients were isolated by the methods of enzymatic digestion and cultured in vitro to the third passage under the microscope to observe their morphology and growth status. The third passage of isolated cells was analysed for the identification of immunophenotype, osteogenic, adipogenic and chondrogenic differentiation.

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  • Minimally manipulated autologous adherent bone marrow cells (ABMCs): a promising cell therapy of spinal cord injury

    Spinal cord injury (SCI) is a devastating ailment that results in drastic life style alterations for the patients and their family members (McDonald and Sadowsky, 2002). Damage post injury causes necrosis, edema, hemorrhage and vasospasm. Post injury, secondary damage is caused by ischemia, excitotoxicity, lipid peroxidation, free radicals production, and inflammation. Collectively, damage to multiple neuronal and glia sub-types leads to severed axonal connections, demyelination and scar tissue formation. Interventions therefore require regeneration of multiple axonal projections to recreate the lost neuronal diversity originally achieved through an elaborate, tightly regulated transcriptional code during development. Neuronal repair and regeneration post injury is impeded due to absence of such supportive environment in the adult spinal cord (Misra et al., 2014).

    Impressive research advances using cell therapies have ushered in an era of new hope and today we are witnessing the translation of studies utilizing mesenchymal stem cells (MSCs) into mainline therapies for patients with SCIs. A testimonial to this trend is the surge in clinical studies using cellular transplantation for SCI (Tetzlaff et al., 2011). A search within (clinical trail.gov) using \"MSCs transplantation\" as search terms yielded ~400 studies, with only 6% of them related to SCI repair. Studies at EU clinical trial registry follow similar trends. Within the SCI domain, the majority of studies (69%) utilize BM-derived cells, followed by adipose tissue-derived MSCs (23%) and umbilical cord-derived cells ([Figure 1]a). While exciting at a first glance, a deeper analysis only highlights the confusion that prevails in the field of adult stem cells. The types of cells used and standards for study design and reporting are far from being well defined, despite organized efforts (Steeves et al., 2007). Given the variability in cell derivation protocols, it is extremely difficult to draw valid conclusions from these different (MSCs) cell therapy studies. Additionally, beyond the registered studies, there is alarming number of studies and treatments that are carried out without any controls or standards for safety and outcome measures, creating wrong perceptions in the public outlook. In this perspective, we have extrapolated the documented studies of cellular therapy for SCI to objectively draw inferences on the mechanisms of injury repair, and provide an outlook for bone marrow (BM)-derived cell therapy in the context of SCI.

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  • Role of PRP and Stem Cell Injections in Osteoarthritic Patients of Knee Joint

    Abstract

    : INTRODUCTION: Osteoarthritis of the knee (also called degenerative joint disease and osteoarthrosis) (4) is the most common joint disease after 50 years of age. It is characterized by progressive loss of articular cartilage (4) with subchondral bone sclerosis, osteophyte formation, inflammation of synovial membrane, and an increase in the synovial fluid with decreased viscosity and lubrication properties One approach to regenerative therapy is to supply affected joints with either autologous chondrocytes or chondrogenic bone marrow-derived mesenchymal stem cells (9) (BMSC) in combinations with platelet rich plasma. MATERIALS AND METHODS: In our study we treated 65 cases of osteoarthritis of knees in different age groups. Inour study moderate to severe arthritis cases were studied. Among 65 cases, 45 were females, 20 were males. Among the test group of 65 cases of age group ranging to 56-87yrs, 45 patients were with unilateral knee joint involvement, 10 patients were with bilateral knee joint involvement. On the other side a Control group consists of 50 cases: 30 with unilateral knee joint involvement, 10 patients with bilateral knee joint involvement.

    RESULTS: Both the groups were observed from time to time and analyzed based on the pain scores at 3 days, 1 week, 4 weeks, 3 months and 6 months intervals. At 3days- No difference in the pain scores and mobility noted in both the groups. At 1 week- Improvement in pain scores with increase in mobility reported in 59 of 65 cases in test group. On the other side, improvement in pain scores reported in 41 of 50 cases in control group. At 4 weeks- Improvement in pain scores reported in 63 of 65 cases in test group. And 44 of 50 cases in control group. At 3 months- Improvement in pain scores reported in 62 cases in test group and 30 cases in control group. At 6 months- Improvement in pain scores reported in 56 cases in test group and 26 cases in control group. CONCLUSION: PRP and stem cells injections in to the osteoarthritic knees, produces good results and safe. If the patient is not opting for surgical procedures and this is the only better treatment modality for controlling the pain and improvement of joint function. Hence use of PRP and stem cells injections in osteoarthritic patients is great value in preventing the further damage of the cartilage. By repairing the damaged cartilage with the PRP and stem cells, pain is greatly reduced, increase in the function of joint and patients will have better quality of life.

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  • Bone Marrow-derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

    Introduction

    Knee osteoarthritis (knee OA) is characterised by joint space narrowing, osteophyte formation, and subchondral sclerosis and manifests primarily as joint pain(1), resulting in the physical disability of patients. Around 40% of people over 70 years of age suffer from this condition(2). Knee OA in particular is a major cause of morbidity and is the primary diagnostic indication for total knee replacement(3), the volume of which continues to grow unabated globally. However, the procedure is a major operation and may pose several complications(4). Recently, scientific evidence has strongly demonstrated that novel treatments can modify or change the disease progression of knee OA(5-8). One potential strategy in osteoarthritis treatment is stem cell based therapy. The fundamental knowledge of stem cells is very important prior to translating this technology into clinical practice. Thus, the objectives of this review are to describe stem cells, including bone marrow derived mesenchymal stem cells (MSCs), and to summarise the recent evidence from animal to clinical studies in stem cell based approaches in treating knee osteoarthritis.

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  • Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit

    Abstract

    The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration.

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  • Treatment of Articular Cartilage Injury Using Mesenchymal Stem Cells.

    Abstract

    Articular cartilage lesions can be a debilitating disease resulting in the development of osteoarthritis (OA). In recent years, mesenchymal stem cell (MSC) strategies combined with the microfracture technique are emerging as a powerful tool for cartilage repair. Even though there are some successful reports of MSCs treatments, many aspects have to be optimized such as best cell source and application method. The interest in this field is growing and randomized controlled trials are needed to show the potential of MSC treatment.

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  • Chondrogenically Primed Mesenchymal Stem Cell-Seeded Alginate Hydrogels Promote Early Bone Formation in Critically-Sized Defects

    Abstract

    Hypertrophic cartilaginous grafts can be engineered in vitro using bone marrow derived Mesenchymal Stem Cells (MSCs). When such engineered tissues are implanted in vivo they have been shown to induce bone formation by recapitulating aspects of the developmental process of endochondral ossification. Alginate, a naturally sourced and biocompatible hydrogel, offers an attractive 3D environment to facilitate the in vitro chondrogenesis of MSCs. Furthermore, such alginate hydrogels can potentially be used to engineer cartilage tissues of scale to promote endochondral bone regeneration in large bone defects. The aim of this study was to investigate the ability of chondrogenically-primed MSC-laden alginate hydrogels to induce healing in two distinct critically-sized defect models. Bone marrow derived MSCs were seeded into alginate hydrogels, chondrogenically primed in vitro in the presence of TGF-β3 and then implanted into either a critically-sized rat cranial or femoral defect. μCT analysis 4 weeks post-implantation revealed significantly higher levels of mineralization within the femoral defects treated with MSC-laden alginate hydrogels compared to untreated empty controls, with similar results observed within the cranial defects. However, any newly deposited bone was generated appositional to the alginate material, and occurred only superficially or where the alginate was seen to degrade. Alginate material was found to persist within both orthotopic locations 8 weeks post-implantation, with its slow rate of degradation appearing to prevent complete bone regeneration. In conclusion, while chondrogenically primed MSC-alginate constructs can act as templates to treat critically-sized defects within bones formed through either intramembranous or endochondral ossification, further optimization of the degradation kinetics of the hydrogel itself will be required to accelerate bone tissue deposition and facilitate complete regeneration of such defects.

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  • Treatment of Knee Osteoarthritis with Autologous Expanded Bone Marrow Mesenchymal Stem Cells: 50 Cases Clinical and MRI Results at One Year Follow-Up

    Abstract

    Knee osteoarthritis is one of the most prevalent joint diseases, causing pain, function loss and disability, leading to a progressive cartilage degeneration induced by biochemical changes in its composition. Current available treatments focus on addressing symptoms and joint replacement is the last treatment option.

    Advanced therapies with mesenchymal stem cells build new expectations to improve the results of OA treatments. MSC applied in animal models, show encouraging results in modulating inflammation and joint cartilage repair. Several studies applied autologous mesenchymal stem cells to treat knee osteoarthritis in humans by means of an intra-articular injection.

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  • Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis

    Abstract

    Osteoarthritis (OA) is a chronic, progressive, and irreversible degenerative joint disease. Conventional OA treatments often result in complications such as pain and limited activity. However, transplantation of mesenchymal stem cells (MSCs) has several beneficial effects such as paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. In addition, MSCs can be differentiated into several cell types, including chondrocytes, OPEN ACCESS Int. J. Mol. Sci. 2015, 16 14962 osteocytes, endothelia, and adipocytes. Thus, transplantation of MSCs is a suggested therapeutic tool for treatment of OA. However, transplanted naׯve MSCs can cause problems such as heterogeneous populations including differentiated MSCs and undifferentiated cells. To overcome this problem, new strategies for inducing differentiation of MSCs are needed. One possibility is the application of microRNA (miRNA) and small molecules, which regulate multiple molecular pathways and cellular processes such as differentiation. Here, we provide insight into possible strategies for cartilage regeneration by transplantation of differentiated MSCs to treat OA patients.

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  • Stem Cell Therapies for Post-Traumatic Arthritis

    Post-traumatic arthritis (PTA) is a common condition that occurs in more than 40% of people who experience significant joint trauma, such as ligament injury, meniscal tear, or intra-articular fracture [1]. PTA is estimated to be responsible for 12% of all osteoarthritis (OA)

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  • Mesenchymal Stem Cell Implantation in Knee Osteoarthritis - An Assessment of the Factors Influencing Clinical Outcomes

    Abstract

    Background: Several clinical studies have reported on cell-based treatment using mesenchymal stem cells (MSCs) for cartilage regeneration in knee osteoarthritis (OA). However, little is known about the factors that influence the clinical outcomes after surgery.

    Purpose/Hypothesis: This study aimed to investigate the clinical outcomes of MSC implantation in patients with knee OA and assess the factors that are associated with clinical outcomes. The hypothesis was that factors may exist that could influence clinical outcomes.

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  • Biomaterial Scaffolds for Mesenchymal Stem Cell Based Therapy Aimed at Tissue Engineering Application for Osteoarthritis

    Abstract

    RDegenerative joint diseases have seen a rise in the past few decades. Among them, the prevalence of Osteoarthritis (OA) is the highest as compared to the other types of arthritis. It involves the degradation of cartilage in joints that ultimately leads to their degeneration. Globally, it affects over 200 million people and the statistics are only expected to increase over the next few decades. The treatment approach for initial stages of OA involves changes in the lifestyle, use of analgesics, NSAIDs and other medications. As the condition worsens, the end point treatment is generally a prosthetic implant followed by surgery. These approaches are short-term and the patients are often found complaining of the post-surgical complications of the invasive methods. This has created the need for less invasive and sustainable treatment approaches. Mesenchymal stem cells (MSCs) have the potential to be differentiated into various kinds of cells making stem cell based therapy an attractive approach for both, researchers and medical experts. We aimed at fabricating biomaterials and microstructures that would provide these MSCs with support and would allow them to organize themselves. The biomaterial and micro-structures fabricated by the \"Layer-by-Layer\"(L-b-l) method exhibited extracellular matrix (ECM) like properties enhancing the adhesion and differentiation of the MSCs. Similar activity has been claimed by researchers of Osaka University who have filed a patent for self-organization for osteochondral regeneration. It was observed that the human MSCs organized themselves better on the biomaterial that we had fabricated for them. We also found that the micro-structures had the potential to give rise to a complex scaffold system.

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  • Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells

    Introduction

    The control of differentiation of mesenchymal stromal/stem cells (MSCs) is crucial for tissue engineering strategies employing MSCs. The purpose of this study was to investigate whether the transcriptional co-factor Yes-associated protein (YAP) regulates chondrogenic differentiation of MSCs.

    Methods

    Expression of total YAP, its paralogue transcriptional co-activator with PDZ-binding motif (TAZ), and individual YAP transcript variants during in vitro chondrogenesis of human MSCs was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). YAP expression was confirmed by western blotting. To determine the effect of high YAP activity on chondrogenesis, C3H10T1/2 MSC-like cells were transduced with human (h)YAP and treated in micromass with bone morphogenetic protein-2 (BMP-2). Chondrogenic differentiation was assessed by alcian blue staining and expression of chondrocyte-lineage genes. BMP signalling was determined by detection of pSmad1,5,8 by western blotting and expression of BMP target genes by quantitative RT-PCR. Finally, YAP and pYAP were detected in mouse embryo hindlimbs by immunohistochemistry.

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  • Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model € 

    Abstract

    This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydorgel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects. This article is protected by copyright. All rights reserved

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  • Human somatic stem cell-based therapy for cartilage regeneration

    Abstract

    Clinical investigations using human somatic tissue derived stem cells for a variety of different diseases have been performed. Neural crest-derived stem cells exhibit somatic organization, can contribute to mesenchymal stem/stromal cells (MSCs) (1) and are used for cartilage treatment, bone reconstruction and anti-inflammatory treatments for diseases. The most common cell source for cartilage treatment is MSCs (2,3). Many clinical studies have used neural crest-derived stem cells (or MSCs) from different tissues and different methodologies. These differences in the generation of somatic tissue-derived stem cells have led to variable results in clinical studies. Although stem cell properties have been poorly characterized, human trials are presently under way.

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