Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches: an Overview

[Abstract] Hydrogel-based nonviral gene delivery constitutes a powerful strategy in various regenerative medicine scenarios, as those concerning the treatment of musculoskeletal, cardiovascular, or neural tissues disorders as well as wound healing. By a minimally invasive administration, these systems can provide a spatially and temporarily defined supply of specific gene sequences into the target tissue cells that are overexpressing or silencing the original gene, which can promote natural repairing mechanisms to achieve the desired effect. In the present work, we provide an overview of the most avant-garde approaches using various hydrogels systems for controlled delivery of therapeutic nucleic acid molecules in different regenerative medicine approaches.This research was funded by Ministerio de Ciencia e Innovación, grant number RTI2018-099389-A-10

Is Myofascial Release Therapy Cost-Effective When Compared with Manual Therapy to Treat Workers’ Mechanical Neck Pains?

[Abstract] Objective: The aim of this study was to do a cost-benefit analysis of myofascial release therapy (MRT) compared to manual therapy (MT) for treating occupational mechanical neck pain. Methods: Variables regarding the outcomes of the intervention were intensity of neck pain, cervical disability, quality of life, craniovertebral angle, and ranges of cervical motion. Costs were assessed based on a social perspective using diary costs. Between-groups differences in average cost, cost-effectiveness, and cost-utility ratios were assessed using bootstrap parametric techniques. The economic cost-benefit evaluation was with regard to an experimental parallel group study design. There were 59 participants. Results: Myofascial released therapy showed significant improvement over MT for cervical mobility (side bending, rotation, and craniovertebral angle). The total cost of MRT was approximately 20% less ( $519.81; 95interval,$1193.67 to $100.31) than that of MT, although this was not statistically significant. Cost-effectiveness and cost-utility ratios showed that MRT could be associated with lower economic costs. Conclusion: With probabilities of 93.9% and 95.8%, MRT seems to be cost-effective for treating mechanical neck pain without the need to add any additional cost to obtain a better clinical benefit. Consequently, we believe it could be included in the clinical practice guidelines of different Spanish health care institutions

Myofascial release therapy in the treatment of occupational mechanical neck pain: a randomized parallel group study

[Abstract] Objective: As myofascial release therapy is currently under development, the objective of this study was to compare the effectiveness of myofascial release therapy with manual therapy for treating occupational mechanical neck pain. Design: A randomized, single-blind parallel group study was developed. The sample (n = 59) was divided into GI, treated with manual therapy, and GII, treated with myofascial release therapy. Variables studied were intensity of neck pain, cervical disability, quality of life, craniovertebral angle, and ranges of cervical motion. Results: At five sessions, clinical significance was observed in both groups for all the variables studied, except for flexion in GI. At this time point, an intergroup statistical difference was observed, which showed that GII had better craniovertebral angle (P = 0.014), flexion (P = 0.021), extension (P = 0.003), right side bending (P = 0.001), and right rotation (P = 0.031). A comparative analysis between therapies after intervention showed statistical differences indicating that GII had better craniovertebral angle (P = 0.000), right (P = 0.000) and left (P = 0.009) side bending, right (P = 0.024) and left (P = 0.046) rotations, and quality of life. Conclusions: The treatment of occupational mechanical neck pain by myofascial release therapy seems to be more effective than manual therapy for correcting the advanced position of the head, recovering range of motion in side bending and rotation, and improving quality of life

Differentiation of Synovial CD-105+ Human Mesenchymal Stem Cells into Chondrocyte-like Cells through Spheroid Formation

[Abstract] Mesenchymal stem cells (MSCs) have the capacity to differentiate into several cell lineages, some of which can generate bone, cartilage, or adipose tissue. The presence of MSCs in the synovial membrane was recently reported. Data from comparative studies of MSCs derived from various mesenchymal tissues suggest that MSCs from synovial membranes have a superior chondrogenesis capacity. Previous chondrogenic differentiation studies have used the total population of MSCs, including cells with several MSC markers, such as CD44, CD90, CD105, or CD73. However the chondrogenic capacity of an individual population of MSCs has not been examined. Our aim was to study the chondrogenic capacity of the cellular MSC subset, CD105+, derived from synovial membrane tissues of patients with osteoarthritis (OA) and normal donors. The tissues were digested with a cocktail of collagenase/dispase and the isolated MSCs were seeded into plates. The subpopulation of CD105+-MSCs was separated using a magnetic separator. The MSCs were then differentiated towards chondrocyte-like cells using a specific medium to promote spheroid formation. Spheroids were collected after 14, 28, and 46 days in chondrogenic medium and stained with hematoxylin, eosin, Safranin O or Alcian blue to evaluate the extracellular matrix. Immunohistochemistry was performed to study collagen types I (COLI) and II (COLII) and aggrecan expression. Phenotypic characterization of the isolated CD105+-MSCs shows that these cells are also positive for CD90 and CD44, but negatives for CD34 and CD45. In addition, this cellular subset expressed Sox-9. Spheroids appeared after 7 days in culture in the presence of chondrogenic medium. Our studies show no differences between MSCs obtained from OA and normal synovial membranes during chondrogenesis. The morphological analysis of spheroids revealed characteristics typical of chondrocyte cells. The intensity of Safranin O, Alcian blue and aggrecan staining was positive and constant throughout the culture period. However, the intensity of COL2 staining was higher at 28 days (84.29 ± 0.1 U) than at 46 days (61.28 ± 01 U), while COL1 staining was not detected in any samples analyzed. These results were confirmed by reverse transcriptase-polymerase chain reaction assays. We conclude that the cellular subset of CD105+-MSCs has chondrogenic capacity. The study also show the similar chondrogenic capacity of CD105+-MSCs cultured from normal and OA synovial membranes. J. Cell. Biochem. 108: 145–155, 2009.Servizo Galego de Saúde; PS07/8

Umbilical Cord as a Mesenchymal Stem Cell Source for Treating Joint Pathologies

[Abstract] Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of life. Regrettably, the regeneration of articular cartilage is a continuing challenge for biomedical research. One of the most promising therapeutic approaches is cell-based tissue engineering, which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured site. The use of healthy chondrocytes has been found to have limitations. A promising alternative cell population is mesenchymal stem cells (MSCs), known to possess excellent proliferation potential and proven capability for differentiation into chondrocytes. The “immunosuppressive” property of human MSCs makes them an important candidate for allogeneic cell therapy. The use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting procedures. An allogeneic cell-based approach would enable MSCs to be isolated from any donor, expanded and cryopreserved in allogeneic MSC banks, providing a readily available source of progenitors for cell replacement therapy. These possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology communities. Our objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.Ministerio de Economía y Competitividad; PLE2009-0144Instituto de Salud Carlos III; CB06-01-004

Alternative protocols to induce chondrogenic differentiation: transforming growth factor-β superfamily

[Abstract] Mesenchymal stem cells (MSCs) are an accepted candidate for cell-based therapy of multiple diseases. The interest in MSCs and their possible application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently, like aggregation and transforming growth factor beta (TGFβ) delivery, hypoxia has been indicated as crucial for complete chondrogenesis. The aim of this study was to test different culture conditions for directing stem cell differentiation into the chondrogenic lineage in vitro by testing different TGFβ superfamily members into the culture media under normoxic conditions. All chondrogenic culture conditions used allowed the differentiation of bone marrow-MSCs (BM-MSCs) into chondrogenic lineage. Chondrogenic induction capacity depended on the growth factor added to the culture media. In particular, the chondrogenic culture condition that better induced chondrogenesis was the medium that included the combination of three growth factors: bone morphogenetic protein-2 (BMP-2), BMP-7 and TGFβ-3. In this culture media, differentiated cells showed the highest levels expression of two markers of chondrogenesis, SOX9 and COL2A1, compared to the control points (p < 0.05, two-tailed t test). In our experimental conditions, the combination of BMP-2, BMP-7 and TGFβ-3 was the most effective in promoting chondrogenesis of BM-MSCs. These results underline the importance of determining in each experimental design the best protocol for in vitro directing stem cell differentiation into the chondrogenic lineage.Galicia. Consellería de Sanidade; PS07/84Ministerio de Ciencia e Innovacion; PLE2009-0144Instituto de Salud Carlos III; PI 08/202

Cell and Tissue Transplant Strategies for Joint Lesions

[Abstract] Articular cartilage lesions that do not disrupt the integrity of subchondral bone are not capable of spontaneous repair. The asymptomatic nature of these lesions leads to articular cartilage degeneration and development of the osteoarthritic process. To avoid joint replacement surgery, several cellular therapies have been developed. These therapies focus on the regeneration of a new tissue, whose structure, biochemistry composition and function should be the same as those of endogenous articular cartilage. Current approaches for interrupting the osteoarthritic process produce a fibrocartilaginous tissue, not articular cartilage. The implantation of autologous chondrocytes and autologous mosaicplasty induces a better quality of articular cartilage; however, both techniques damage the existing cartilage because of the need to harvest large numbers of chondrocytes or to extract an osteochondral cylinder for implantation. While stem cells are a promising tool for repairing articular cartilage, their use is in an early experimental stage at this time. Although studies of cell therapy have shown clinical and functional improvement in joints, the ability to regenerate articular cartilage that resists the degeneration process remains elusive.Xunta Galicia; PGIDIT06PXIC916175PNInstituto de Salud Carlos III; CB06/01/004