A clinically defined and xeno-free hydrogel system for regenerative medicine

Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity oftransdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo.

Bioactive molecules derived from umbilical cord mesenchymal stem cells

Regenerative Medicine and Rehabilitation Therapy in the Canine

<h3>Introduction and history</h3> While regenerative medicine may seem like a novel intervention in the chronic pain armamentarium, its evolution and in a sense its definition has been intricately related to...

Use of stem cell-based therapies in tissue engineering and regenerative medicine is hindered by efficient means of directed differentiation. For pluripotent stem cells, an initial critical differentiation event is specification to one of three germ lineages: endoderm, mesoderm, and ectoderm. Differentiation is known to be regulated by numerous extracellular and intracellular factors, but the role of the cytoskeleton during specification, or early differentiation, is still unknown. In these studies, we used agonists and antagonists to modulate actin polymerization and the actin-myosin molecular motor during spontaneous differentiation of embryonic stem cells in embryoid bodies. We found that inhibiting either actin polymerization or actin-myosin interactions led to a decrease in differentiation to the mesodermal lineage and an increase in differentiation to the endodermal lineage. Thus, targeting processes that regulate cytoskeletal tension may be effective in enhancing or inhibiting differentiation towards cells of the endodermal or mesodermal lineages, which include hepatocytes, islets, cardiomyocytes, endothelial cells, and osteocytes. Therefore, these fundamental findings demonstrate that modulation of the cytoskeleton may be useful in production for a range of cell-based therapies, including for liver, pancreatic, cardiac, vascular, and orthopedic applications.

Topographic effect on human induced pluripotent stem cells differentiation towards neuronal lineage

Dietary phytochemical approaches to stem cell regulation

Chapter 1 - Genitourinary tissue engineering: Promises, advances, and challenges

Passive microfluidic devices for cell separation

Tissue progenitor cells are an attractive target for regenerative therapy. In various organs, bone marrow cell (BMC) therapy has shown promising preliminary results, but to date no definite mechanism has been demonstrated to account for the observed benefit in organ regeneration. Tissue injury and regeneration is invariably accompanied by macrophage infiltration, but their influence upon the progenitor cells is incompletely understood, and direct signaling pathways may be obscured by the multiple roles of macrophages during organ injury. We therefore examined a model without injury; a single i.v. injection of unfractionated BMCs in healthy mice. This induced ductular reactions (DRs) in healthy mice. We demonstrate that macrophages within the unfractionated BMCs are responsible for the production of DRs, engrafting in the recipient liver and localizing to the DRs. Engrafted macrophages produce the cytokine TWEAK (TNF-like weak inducer of apoptosis) in situ. We go on to show that recombinant TWEAK activates DRs and that BMC mediated DRs are TWEAK dependent. DRs are accompanied by liver growth, occur in the absence of liver tissue injury and hepatic progenitor cells can be isolated from the livers of mice with DRs. Overall these results reveal a hitherto undescribed mechanism linking macrophage infiltration to DRs in the liver and highlight a rationale for macrophage derived cell therapy in regenerative medicine.

Because of their ease of isolation and relative abundance, adipose-derived mesenchymal stem cells (ASCs) are a particularly attractive autologous cell source for various therapeutic purposes. ASCs retain a high proliferation capacity in vitro and have the ability to undergo extensive differentiation into multiple cell lineages. Moreover, ASCs secrete a wide range of growth factors that can stimulate tissue regeneration. Therefore, the clinical use of ASCs is feasible. However, the potential of ASCs differs depending on the donor’s medical condition, including diseases such as diabetes. Recent studies demonstrated that ASCs from diabetic donors exhibit reduced proliferative potential and a smaller proportion of stem cell marker-positive cells. Therefore, to ensure the success of regenerative medicine, tissue engineering methods must be improved by the incorporation of factors that increase the proliferation and differentiation of stem/progenitor cells when autologous cells are used. Platelet-rich plasma (PRP), which contains high levels of diverse growth factors that can stimulate stem cell proliferation and cell differentiation in the context of tissue regeneration, has recently been identified as a biological material that could be applied to tissue regeneration. Thus, co-transplantation of ASCs and PRP represents a promising novel approach for cell therapy in regenerative medicine. In this review, we describe the potential benefits of adding PRP to ASCs and preclinical and clinical studies of this approach in various medical fields. We also discuss the mechanisms of PRP action and future cell-based therapies using co-transplantation of ASCs and PRP.

The success of retinal cell-based therapy in regenerative medicine has many obstacles to overcome. One of the foremost barriers is acceptance of the retinal transplant in the subretinal space of the eye by the host’s immune system. Ocular immune privilege exists in several compartments of the eye including the subretinal space. However, immunologic privilege is a dynamic phenomenon that can be breached by the underlying disease and/or the host immune response. The success of retinal transplantation is not only dependent on the site of engraftment but also on the type of tissue/cell transplanted. The complex immunologic interaction between host, site of transplantation, and cell type transplanted will ultimately determine the potential of retinal cell-based therapy for the treatment of several retinal diseases. There is enormous promise for regenerative medicine to treat retinal diseases and preserve vision, but important issues still need to be resolved before translational clinical use.

Polysaccharide-based hydrogels have emerged as indispensable materials in tissue engineering and wound healing, offering a unique combination of biocompatibility, biodegradability, and structural versatility. Indeed, their three-dimensional polymeric network and high water content closely resemble the natural extracellular matrix, creating a microenvironment for cell growth, differentiation, and tissue regeneration. Moreover, their intrinsic biodegradability, tunable chemical structure, non-toxicity, and minimal immunogenicity make them optimal candidates for prolonged drug delivery systems. Notwithstanding numerous advantages, these polysaccharide-based hydrogels are confronted with setbacks such as variability in material qualities depending on their source, susceptibility to microbial contamination, unregulated water absorption, inadequate mechanical strength, and unpredictable degradation patterns which limit their efficacy in real-world applications. This review summarizes recent advancements in the application of polysaccharide-based hydrogels, including cellulose, starch, pectin, zein, dextran, pullulan and hyaluronic acid as innovative solutions in wound healing, drug delivery, tissue engineering, and regenerative medicine. Future research should concentrate on optimizing hydrogel formulations to enhance their effectiveness in regenerative medicine and antimicrobial therapy.

Regenerative medicine and tissue engineering are now expanding to practically all healthcare fields, including cardiac, corneal, nerve, vascular and liver tissue engineering and regeneration [Bracaglia LG, 2017]. Favorable government regulatory framework, continuous technology advancements and increasing research funding drive the market for alternative regenerative medicine therapies. Global tissue engineering market is expected to reach USD 11.53 billion by 2022, according to a new report by Grand View Research, Inc (2016). Tissue engineering combines cells, biomaterials and growth factors to support and regenerate the biological tissues. Three key components are needed for tissue engineering – cells, growth factors and scaffolds. Whereas cells produce tissue matrix, scaffold provides the appropriate environment for cells to effectively accomplish their missions. The function of growth factors is to facilitate and promote cells to regenerate new tissue [Spurlin JW 3rd, 2017]. Medical company ilaya® uses tissue engineering and regenerative medicine approaches in the clinical applications, such as treatment of critical sized bone defects and avascular necrosis (AVN) . METHODS. To fabricate 3D-TEBE (three-dimensional tissue-engineered bone equivalent) we used devitalized allogeneic/xenogeneic bone (blocks and chips) seeded with autologous cultured cells: bone marrow-derived MSCs alone or in mix with periosteum progenitor cells (PPCs, 3:1), or with PPCs and peripheral blood endothelial progenitor cells (EPCs, 3:1:1) depending on bone defect size. Quality assurance of cell seeded 3D-TEBE was done via combined staining with FDA/PI and histological analysis (H&amp;E). New bone formation was assessed by the radiographic examination. RESULTS. Eighteen patients had the AVN III/IV by Steinberg, 11 of them had cystic bone reconstruction sites. In 8 patients, AVN corresponded to stage IV/V with subchondral fracture and deformation of the femoral head (26 patients in total). In AVN patients bone structure restoration was observed in 94.4% and endoprosthesis surgery was no more actual for 90.9%. Bone integrity was successfully restored in 39 combat related casualties (42 critical sized bone defects). FDA/PI staining, and histological analysis of 3D-TEBE samples showed their regular seeding with viable cells. Histological analysis of 3D-TEBE biopsies 3 months after transplantation showed their intensive remodeling and immature bone tissue formation. Thereof, the 3D-TEBE transplantation is able to restore bone integrity and greatly reduce, as compared with conventional cure methods, patient’s rehabilitation period. Conclusions. The 3D-TEBE transplantation is able to restore bone integrity and greatly reduce, as compared with conventional cure methods, patient’s rehabilitation period.

Until recently, culturing human pluripotent stem cells was hampered by three prominent technical problems: a high degree of unwanted cellular stress when the cells are passaged, unacceptably low cloning efficiency and poor recovery of cryopreserved stocks. This review discusses recent developments that address these problems. A major focus of the review is the use of p160 Rho-associated coiled-coil kinase inhibitors for improving both the cloning efficiency and the recovery of cryopreserved human embryonic stem cells and human induced pluripotent stem cells. An underlying theme of this review is that the three problems have a common cause: separation of human pluripotent stem cells from one another increases cellular stress, which greatly decreases their viability unless special steps are taken.