Functional evaluation of skeletal muscle regeneration following severe crush trauma and the therapeutic application of specialized tissue engineering in the rat

Introduction: Skeletal muscle trauma is a common condition which may result in long term pain and disability. Despite the pool of muscle-specific stem cells termed satellite cells, which are stimulated to proliferate, grow and differentiate to repair muscle fibers upon injury, return to pre-injury function is often impossible. We hypothesized that the transplantation of Mesenchymal Stromal Cells (MSCs) in a synthetic niche supplemented by stimulatory growth factors may support the regenerative process through paracrine modulation of the post-traumatic microcellular environment Methods: A crushed-muscle injury model was implemented in rats. Upon completion, rats received either intramuscular Injections of the growth factors (GF) Insulin Growth Factor-1 and Vascular Endothelial Growth Factor and/or autologous MSCs which had previously been harvested in a bone marrow aspiration, or a specially engineered porous Alginate enriched with the before mentioned growth factors and/or seeded with MSCs. Animals were sacrificed at 7-, 28- and 56 days following trauma and their fast twitch- and tetanic contraction forces were measured via an electromechanical stimulatory device. Results: All experimental groups showed significant decreases in contraction strength at day 7 following injury, with little difference amongst groups. On the contrary, fast twitch and tetanic contraction forces differed significantly between the Alginate-alone control group and the groups transplanted with with Alginates seeded with MSCs and Alginates enriched with GFs and seeded with MSCs at day 28. The highest relative force was found in the latter group, which differed significantly from the others (p (Alginate) <0.001; p (Alginate + GFs) = 0.003). No significant increases in muscle force could be observed in between the groups evaluated at 28 days following trauma and the groups evaluated at 56 days following trauma. Conclusion: We could confirm that the transplantation of a porous Alginate enriched with growth factors and seeded with autologous Mesenchymal Stromal Cells resulted in significantly improved functional outcomes. Tissue engineering, which relies on the transplantation of cells and growth factors conducive of regeneration seeded on scaffolds which support their survival and release into the microcellular environment, may be a solution in particular to nosocomial damage created by incisions necessary during a surgical procedure.Einleitung: Schwere Skelettmuskeltraumata sind ein häufiges klinisches Problem was zu langfristigen Schmerzen und eingeschränkter Mobilität führen kann. Trotz des Pools an muskelspezifischen Stammzellen, die als Satellitenzellen bezeichnet werden, die zur Proliferation, zum Wachstum und zur Differenzierung stimuliert werden, um Muskelfasern nach einer Verletzung zu reparieren, ist die Rückkehr zur Vorverletzungsfunktion oft unmöglich. Wir stellten die Hypothese auf, dass die Transplantation von mesenchymalen Stromalzellen in einem flexiblen Konstrukt, ergänzt durch stimulierende Wachstumsfaktoren, den regenerativen Prozess durch parakrine Modulation der posttraumatischen Mikrozellularumgebung unterstützen kann. Methodik: Es wurde Ratten ein Quetschtrauma des Skelettmuskels zugefügt. Posttraumatisch erhielten die Ratten entweder intramuskuläre Injektionen der Wachstumsfaktoren Insulin- Wachstumsfaktor-1 und des vaskulär-endothelialem Wachstumsfaktors und / oder autologe mesenchymale Stromalzellen, die zuvor in einer Knochenmarkaspiration gewonnen worden waren, oder ein speziell konstruiertes poröses Alginat, angereichert mit den eben genannten Wachstumsfaktoren und / oder mit mesenchymalen Stromalzellen. Die fast twitch sowie die tetanische Kontraktionskraft der Tiere wurden an den Tagen 7, 28 und 56 nach dem Trauma mittels einer elektromechanischen Stimulationsvorrichtung gemessen. Ergebnisse: Alle Versuchsgruppen zeigten am Tag 7 nach der Verletzung eine signifikante Abnahme der Kontraktionskraft, mit geringen Unterschieden zwischen den einzelnen Gruppen. Im Gegensatz dazu unterschieden sich die Kontraktionskräfte zwischen der Kontrollgruppe, der leere Alginate transplantiert wurden, und der mit Wachstumsfaktoren und/oder Stromalzellen bereichterten Alginaten transplantierten Gruppen am Tag 28 nach der Verletzung signifikant. Die höchste Kraft wurde in der Versuchsgruppe gefunden, in der Alginate mit Wachtumsfaktoren und mesenchymalen Stammzellen transplantiert wurden, gefunden. Sie hob sich signifikant von den anderen ab (p (Alginat) <0,001; p (Alginat + GF) = 0,003). Zwischen den Versuchsgruppen, die 28 Tage nach dem Trauma ausgewertet wurden, und den Gruppen, die 56 Tage nach dem Trauma ausgewertet wurden, konnte keine signifikante Zunahme der Muskelkraft beobachtet werden. Schlussfolgerung: Wir konnten bestätigen, dass die Transplantation eines mit Wachstumsfaktoren angereicherten und mit autologen mesenchymalen Stammzellen besetzten porösen Alginats zu signifikant verbesserten funktionellen Ergebnissen führt. Spezialisiertes Tissue Engineering, das auf der Transplantation von Zellen und wachstumsfördernden Faktoren beruht die mittels eines flexiblen Biomaterials transplantiert werden können, dürfte eventuell eine Lösung für nosokomiale Muskelschäden sein, die während eines chirurgischen Eingriffs entstehen können

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

Malnutrition and starvation’s possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality

Effect of Steroid-Soaked Gelatin Sponge on Soft Tissue Swelling Following Anterior Cervical Discectomy and Fusion: A Radiographic Analysis

Study Design Retrospective radiological review and analysis of 79 patients who underwent primary anterior cervical discectomy and fusion (ACDF) of 2 or 3 levels between 2011 and 2013. Purpose This study aimed to determine the effect of the local placement of a steroid-soaked gelatin sponge after ACDF on prevertebral soft tissue swelling. Overview of Literature Although ACDF has become a popular choice for cervical fusion, the surgical involvement of the delicate anatomy of the neck frequently results in tissue irritation and edema. Swelling of the prevertebral soft tissue may consequently lead to mild-to-severe complications, ranging from dysphonia to dyspnea. Methods Out of the 79 patients who underwent primary ACDF, 52 received a gelatin sponge soaked with 40 mg of Depo-Medrol placed adjacent to the operated cervical levels. Prevertebral soft tissue swelling was detected using postoperative lateral X-ray. The radiographic values were compared to those of 27 patients who did not receive the treatment. Results Soft tissue swelling was markedly decreased in patients who received the placement of the steroid-soaked gelatin sponge next to their fused levels after surgery compared with that in patients who did not receive it. No complications were documented with the use of steroids. Conclusions The placement of a steroid-soaked gelatin sponge markedly reduces postoperative soft tissue swelling following 2- or 3-level primary ACDF

ALX1‐related frontonasal dysplasia results from defective neural crest cell development and migration

[Image: see text

ALX1‐related frontonasal dysplasia results from defective neural crest cell development and migration

Abstract A pedigree of subjects presented with frontonasal dysplasia (FND). Genome sequencing and analysis identified a p.L165F missense variant in the homeodomain of the transcription factor ALX1 which was imputed to be pathogenic. Induced pluripotent stem cells (iPSC) were derived from the subjects and differentiated to neural crest cells (NCC). NCC derived from ALX1L165F/L165F iPSC were more sensitive to apoptosis, showed an elevated expression of several neural crest progenitor state markers, and exhibited impaired migration compared to wild‐type controls. NCC migration was evaluated in vivo using lineage tracing in a zebrafish model, which revealed defective migration of the anterior NCC stream that contributes to the median portion of the anterior neurocranium, phenocopying the clinical presentation. Analysis of human NCC culture media revealed a change in the level of bone morphogenic proteins (BMP), with a low level of BMP2 and a high level of BMP9. Soluble BMP2 and BMP9 antagonist treatments were able to rescue the defective migration phenotype. Taken together, these results demonstrate a mechanistic requirement of ALX1 in NCC development and migration