Turkey Ovarian Tissue Transplantation: Effects of Surgical Technique on Graft Attachment and Immunological Status of the Grafts 6 Days Post-surgery

Background: Biobanked poultry ovaries can be revived via transplantation, into a recipient female, which upon maturity will produce donor-derived progeny. Previously, a large portion of these recipients also produced recipient-derived progeny, making them gonadal chimeras. These were potentially created when portions of the recipient’s ovary were inadvertently left behind. Completely removing the recipient ovary would solve this problem, however, leaving a portion of the recipient’s ovary may have inadvertently increased the transplant attachment rate by providing a damaged area for the transplant to attach too. To test this hypothesis in the turkey, we removed various portions (33% to 100%) of recipient ovarian tissue and determined the transplant attachment rate. Furthermore, the use of the abdominal air sac membrane as an additional anchoring point was tested. Finally, the immunological status of the grafts was evaluated by analyzing the presences of CD3 and MUM-1 (T and B cell markers), 6 days post-surgery.Results: The overall attachment rate of transplants was 91% (32/35), while the average size of the transplants was 4.2 ± 0.6 mm2. There was no difference (P > 0.05) in the attachment rates, or transplant size between groups with varying amounts of recipent tissue removed, or by using the abdominal air sac membrane as an anchor. However, all transplants were infiltrated by large numbers of T and B cells. This was shown by a high (P ≤ 0.001) percentage of CD3-positive immunostained cytoplasmic area (49.78 ± 3.90%) in transplants compared to remnant recipient tissue (0.30 ± 0.10%), as well as a high (P ≤ 0.001) percentage of MUM-1-positive immunostained nuclear area (9.85 ± 1.95%) in transplants over remnant recipient tissues (0.39 ± 0.12%).Conclusions: This study showed that neither the portion of the recipient ovary left behind nor the use of the abdominal air sac membrane affected the rate of attachment or the amount of donor tissue that attached. Thus, we recommend removing the entire recipient ovary to prevent gonadal chimeras. The high levels of lymphocytes within the grafts indicate possible tissue rejection, which could be overcome via immunosuppression with or without histocompatibility matching between donors and recipients.

Decellularized dermis extracellular matrix alloderm mechanically strengthens biological engineered tunica adventitia-based blood vessels

The ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. We hypothesized that an ECM material would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and FDA-approved. We evaluated the commercially-available decellularized skin dermis ECM Alloderm for efficacy in providing structure to BEBVs. Alloderm was incorporated into our lab’s unique protocol for generating BEBVs, using fibroblasts to establish the adventitia. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg. Total collagen and fiber maturity were significantly increased due to the presence of the Alloderm material. Vessels cultured for 4 weeks maintained mechanical and structural integrity. Low probability of thrombogenicity was confirmed with a negative platelet adhesion test. Vessels were able to be endothelialized. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.

Decellularized Dermis Extracellular Matrix Alloderm as a Scaffold for Biological Engineered Blood Vessels

The ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. Current methods of mechanical conditioning to encourage extracellular matrix (ECM) deposition requires weeks to months, impeding translation. We hypothesized that an ECM scaffold would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and is FDA-approved. We evaluated the commercially available decellularized skin dermis ECM called Alloderm for its efficacy in providing structure to biological engineered blood vessels. Alloderm was seeded with fibroblast cells typically found in the adventitia during integration into our lab’s unique protocol for generating BEBVs. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg. Total collagen and fiber maturity were significantly increased due to the presence of the scaffolding material. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.

Induced pluripotent Stem Cells: Where we are currently?

Induced Pluripotent Stem Cells (iPSCs) are a type of pluripotent stem cells generated by reprogramming an adult somatic cell genome to the stage of a pluripotent stem cell in vitro by inducing a forced expression of specific transcription factors that are important for the maintenance of pluripotency. The iPSCs seem to be very similar to Embryonic Stem Cells (ESCs) in terms of morphology, cell surface markers and gene expression levels, but recent studies have demonstrated some differences between the two cell types. However, iPSCs might have potential application in regenerative medicine, transplantation, drug testing, disease modelling, and avoidance of tissue rejection and with less ethical concern than ESCs. This paper aims to present the most important characteristics of iPSCs which have therapeutic significance.

Fabrication of Cellulose Acetate/Cellulose-HA Composite Films for Bone Fixation

Bone is a rigid and constantly remodeling organ, a type of tissue which provides support and protects organs in the body, and together they form the skeleton [1]. Materials generally used for implants bear tissue rejection and produce toxins on degradation [2]. Our objective is to synthesize a biocompatible composite of Hydroxyapatite (HA) and Cellulose using Cellulose Acetate as a matrix which mimics the properties of natural bone that can be used for bone replacements. Bone is composed of calcium phosphate (HA) and collagen, which gives bone desired properties [3]. Hydroxyapatite is the inorganic mineral found in the bone and is preferred due to its mechanical properties, biocompatibility, slow degradation in physiological environment and bioactivity [4]. Cellulose, structural component in plants is similar in properties to collagen therefore the properties of cellulose [4], HA and cellulose acetate are exploited to achieve our results. The experimental procedure is divided into two major steps; extraction of cellulose microfibers (CMF) from cotton followed by dispersion of cellulose and HA in cellulose acetate then casting membranes of the composite.

Robust Axonal Regeneration in a Mouse Vascularized Composite Allotransplant Model Undergoing Delayed Tissue Rejection

Background: Nerve regeneration in vascularized composite allotransplantation (VCA) is not well understood. Allogeneic transplant models experience complete loss of nerve tissue and axonal regeneration without immunosuppressive therapy. The purpose of this study was to determine the impact of incomplete immunosuppression on nerve regeneration. Methods: In this study, transgenic mice (4 groups in total) with endogenous fluorescent protein expression in axons (Thy1-YFP) and Schwann cells (S100-GFP) were used to evaluate axonal regeneration and Schwann cell (SC) migration in orthotopic-limb VCA models with incomplete immunosuppression using Tacrolimus (FK506). Survival and complication rates were assessed to determine the extent of tissue rejection. Nerve regeneration was assessed using serial imaging of axonal progression and SC migration and viability. Histomorphometry quantified the extent of axonal regeneration. Results: Incomplete immunosuppression with FK506 resulted in delayed rejection of skin, muscle, tendon, and bone in the transplanted limb. In contrast, the nerve demonstrated robust axonal regeneration and SC viability based on strong fluorescent protein expression by SCs and axons in transgenic donors and recipients. Total myelinated axon numbers measured at 8 weeks were comparable in all VCA groups and not statistically different from the syngeneic donor control group. Conclusions: Our data suggest that nerve and SCs are much weaker antigens compared with skin, muscle, tendon, and bone in VCA. To our knowledge, this study is the first to prove the weak antigenicity of nerve tissue in the orthotopic VCA mouse model.

Vasopressin: the missing link for preeclampsia?

Preeclampsia is a devastating cardiovascular disorder of late pregnancy, affecting 5–7% of all pregnancies and claiming the lives of 76,000 mothers and 500,000 children each year. Various lines of evidence support a “tissue rejection” type reaction toward the placenta as the primary initiating event in the development of preeclampsia, followed by a complex interplay among immune, vascular, renal, and angiogenic mechanisms that have been implicated in the pathogenesis of preeclampsia beginning around the end of the first trimester. Critically, it remains unclear what mechanism links the initiating event and these pathogenic mechanisms. We and others have now demonstrated an early and sustained increase in maternal plasma concentrations of copeptin, a protein by-product of arginine vasopressin (AVP) synthesis and release, during preeclampsia. Furthermore, chronic infusion of AVP during pregnancy is sufficient to phenocopy essentially all maternal and fetal symptoms of preeclampsia in mice. As various groups have demonstrated interactions between AVP and immune, renal, and vascular systems in the nonpregnant state, elevations of this hormone are therefore positioned both in time (early pregnancy) and function to contribute to preeclampsia. We therefore posit that AVP represents a missing mechanistic link between initiating events and established midpregnancy dysfunctions that cause preeclampsia.

IFNγ modulates human immunoglobulin receptor expression in lipoaspirate-derived mesenchymal stem cells

Background: Mesenchymal stem cell (MSC) has been reported to have immunomodulator capacity against autoimmune diseases and to prevent allogenic tissue rejection. Many studies revealed that MSC’s inhibit T cell proliferation and induce immunosuppressive condition through the production of prostaglandins, and interleukin-10. In addition, MSC was reported to reduce circulating autoantibody in autoimmune patients following MSC transfusion. So far, there has been no report stating the presence of Fc receptors (receptors for immunoglobulin) on MSCs. The aim of this study was to reveal the expression of FcγRs in lipoaspirate-derived MSCs by measuring transcription of FcγR mRNA and whether the expression can be modulated.Methods: Lipoaspirate-derived MSCs were cultured in suitable medium and confirmed to be MSCs according to the criteria published by International Society for Cellular Therapy. Total mRNA of MSCs was isolated, and detection of human FcγRI, FcγRIIA and FcγRIIB mRNA was performed. Further, modulation of the expression was tested using heat aggregated gamma globulin (HAGG) and interferon (IFN)γ.Results: FcγRs mRNA was detected in the first passage of MSCs. However, the expression was no longer present after more than 4 passages. Further, increased level of FcγRI and FcγRIIA mRNA expression was detected with the addition of IFNγ in the culture. This preliminary finding opens a new insight for the understanding of interaction between MSCs and immunoglobulin G through FcγRs.Conclusion: Lipoaspirate-derived MSCs express FcγRs, and the expression is modulated by IFNγ.

Biological Effects ofSpirulina(Arthrospira) Biopolymers and Biomass in the Development of Nanostructured Scaffolds

Spirulinais produced from pure cultures of the photosynthetic prokaryotic cyanobacteriaArthrospira. For many years research centers throughout the world have studied its application in various scientific fields, especially in foods and medicine. The biomass produced fromSpirulinacultivation contains a variety of biocompounds, including biopeptides, biopolymers, carbohydrates, essential fatty acids, minerals, oligoelements, and sterols. Some of these compounds are bioactive and have anti-inflammatory, antibacterial, antioxidant, and antifungal properties. These compounds can be used in tissue engineering, the interdisciplinary field that combines techniques from cell science, engineering, and materials science and which has grown in importance over the past few decades.Spirulinabiomass can be used to produce polyhydroxyalkanoates (PHAs), biopolymers that can substitute synthetic polymers in the construction of engineered extracellular matrices (scaffolds) for use in tissue cultures or bioactive molecule construction. This review describes the development of nanostructured scaffolds based on biopolymers extracted from microalgae and biomass fromSpirulinaproduction. These scaffolds have the potential to encourage cell growth while reducing the risk of organ or tissue rejection.

SmartHand: A Sense of Assistive Devices

Amputees have often faced social stigma attributable to their visible limb loss or use of artificial substitutions. In recent years, the use of prosthetics has become much more advanced, particularly in the field of sensory prostheses. One such assistive device, a new prototype technology known as the SmartHand, has recently been featured on several news networks. It is through this discussion that the SmartHand will be reviewed and compared with existing platforms that include myoelectric prostheses and targeted muscle reinnervation. Use of the SmartHand has been noted as having increased levels of competence in and improved the quality of life of its users. These conclusions also bring to light the scientific barriers that are faced, primarily with respect to tissue rejection. The cost benefit analysis of such a device may also produce conflicting data, thereby making it difficult to implement this device on a larger scale. Despite these problems, the SmartHand represents one of the most scientifically advanced assistive devices available in today’s market, whose usefulness for amputees is undeniable.