A fresh look at augmenter of liver regeneration in rats.

Augmenter of liver regeneration (ALR) is a hepatotrophic protein originally identified by bioassay in regenerating rat and canine livers following partial hepatectomy and in the hyperplastic livers of weanling rats, but not in resting adult livers. The ALR gene and gene product were subsequently described, but little is known about the cellular/subcellular sites of ALR synthesis in the liver, or about the release and dissemination of the peptide. To obtain this information in rats, we raised antibodies in rabbits against rat ALR for development of an enzyme-linked immunosorbent assay (ELISA). ALR concentrations were then determined in intact livers of unaltered weanling and adult rats; in regenerating residual liver after partial hepatectomy; in cultured hepatocytes and nonparenchymal cells (NPCs); and in culture medium and serum. ALR in the various liver cells was localized with immunohistochemistry. In addition, hepatic ALR and ALR mRNA were assayed with Western blotting and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. The hepatocyte was the predominant liver cell in which ALR was synthesized and stored; the cultured hepatocytes secreted ALR into the medium in a time-dependent fashion. Contrary to previous belief, the ALR peptide and ALR mRNA were present in comparable concentrations in the hepatocytes of both weanling and resting adult livers, as well as in cultured hepatocytes. A further unexpected finding was that hepatic ALR levels decreased for 12 hours after 70% hepatectomy in adult rats and then rose with no corresponding change in mRNA transcripts. In the meantime, circulating (serum) ALR levels increased up to 12 hours and declined thereafter. Thus, ALR appears to be constitutively expressed in hepatocytes in an inactive form, and released from the cells in an active form by unknown means in response to partial hepatectomy and under other circumstances of liver maturation (as in weanling rats) or regeneration

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Applications and Limitations of 3D Bioprinters in Tissue Culturing: A Review

3D bioprinting is an advanced technology that uses different biomaterial like hydrogels and bio-inks to develop artificial tissue cells and organs. There are three types of bioprinting techniques: Jetting-based bioprinting, extrusion based bioprinting, and integrated bioprinting. Biomaterials used in 3D bioprinter should have some ideal characteristics such as they should be biocompatible, printable, and provide mechanical and structural properties. There are different types of bio-inks, hydrogels, and growth factors used to overcome the crisis of organ shortage. Bioprinting technology is essential for the development of eleven organ systems as there is a need for organ replacement and tissue regeneration. It is possible to make complex tissue culture structures by using 3D bioprinting. The mixture of biomaterial and living cells used for bioprinting is called bio-inks. Hydrogels are one of the ideal components of biomaterials as it has similar characteristics as natural extracellular matrix and provides a hydrated environment for cells to divide. Generation and transportation of many tissues, including skin, heart tissues, cartilaginous constructs, and tracheal tissues is done by 3D bioprinting. It is used for research purposes, drug testing, and drug discovery. But our focus is to highlight the applications of 3D bioprinters in tissue engineering and the development of organ systems. Skin tissues have also been engineered to overcome complex skin treatment procedures and to save time and cost

Reconstitution of Kidney Side Population Cells after Ischemia-Reperfusion Injury by Self-Proliferation and Bone Marrow-Derived Cell Homing

The aim of this study was to examine the contribution of side population (SP) cells from kidney and bone marrow for reconstitution of kidney SP pools after ischemia-reperfusion injury (IRI). The SP and non-SP cells in kidneys following IRI were isolated and serially assessed by fluorescence-activated cell sorting. The apoptosis, proliferation, phenotype, and paracrine actions of SP cells were evaluated in vitro and in vivo. Results indicated that the SP cells from ischemic kidney were acutely depleted within one day following renal IRI and were progressively restored to baseline within 7 days after IRI, through both proliferation of remaining kidney SP cells and homing of bone marrow-derived cells to ischemic kidney. Either hypoxia or serum deprivation alone increased apoptosis of SP cells, and a combination of both further aggravated it. Furthermore, hypoxia in vivo and in vitro induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1α in kidney SP but not non-SP cells. In summary, these results suggest that following renal IRI, kidney SP cells are acutely depleted and then progressively restored to baseline levels by both self-proliferation and extrarenal source, that is, bone marrow-derived cell homing

Artificial restoration of the linkage between laminin and dystroglycan ameliorates the disease progression of MDC1A muscular dystrophy at all stages

Laminin-α2 deficient congenital muscular dystrophy, classified as MDC1A, is a severe progressive muscle-wasting disease that leads to death in early childhood. MDC1A is caused by mutations in lama2, the gene encoding the laminin-α2 chain being part of laminin-2, the main laminin isoform present in the extracellular matrix of muscles and peripheral nerves. Via selfpolymerization, laminin-2 forms the primary laminin scaffold and binds with high affinity to α- dystroglycan on the cell surface, providing a connection to the cytoskeleton via the transmembranous protein β-dystroglycan. Deficiency in laminin-α2 leads to absence of laminin-2 and to upregulation of laminin-8, a laminin isoform that cannot self-polymerize and does not bind to α-dystroglycan. Therefore, in laminin α2-deficient muscle the chain of proteins linking the intracellular contractile apparatus via the plasma membrane to the extracellular matrix is interrupted. Consequently, muscle fibers loose their stability and degenerate what finally leads to a progressive muscle wasting. In previous studies, we have shown that a miniaturized form of the extracellular matrix protein agrin, which is not related to the disease-causing lama2 gene and was designed to contain highaffinity binding sites for the laminins and for α-dystroglycan, was sufficient to markedly improve muscle function and overall health in the dyW-/- mouse model of MDC1A. In a follow-up study we provided additional evidence that mini-agrin, both increases the tolerance to mechanical load but also improves the regeneration capacity of the dystrophic muscle. We now report on our progress towards further testing the use of this approach for the treatment of MDC1A. To test whether mini-agrin application after onset of the disease would still ameliorate the dystrophic symptoms, we have established the inducible tetracycline-regulated “tet-off” expression system in dyW-/- mice to temporally control mini-agrin expression in skeletal muscles. We show that mini-agrin slows down the progression of the dystrophy when applied at birth or in advanced stages of the disease. However, the extent of the amelioration depends on the dystrophic condition of the muscle at the time of mini-agrin application. Thus, the earlier miniagrin is applied, the higher is the profit of its beneficial properties. In addition to gene therapeutical approaches, the increase of endogenous agrin expression levels in skeletal muscles by pharmacologically active compounds would be a safe and promising strategy for the treatment of MDC1A. To evaluate the potential and pave the way to further expand on the development of such a treatment, we determined whether full-length agrin ameliorates the dystrophic phenotype to a comparable extent as it was observed by application of mini-agrin. We provide evidence that constitutive overexpression of chick full-length agrin in dyW-/- muscle ameliorates the dystrophic phenotype, although not as pronounced as mini-agrin does. In conclusion, our results are conceptual proof that linkage of laminin to the muscle fiber membrane is a means to treat MDC1A at any stage of the disease. Our findings definitely encourage to further expanding on this therapeutic concept, especially in combination with treatment using functionally different approaches. Moreover, these experiments set the basis for further developing clinically feasible and relevant application methods such as gene therapy4 and/or the screening of small molecules able to upregulate production of agrin in muscle

Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation

Xenotransplantation

Recently, remarkable progress has been made in the area of preclinical xenotransplantation experiments. Surprisingly, a heterotopic heart from the gene-editing pig continued to beat for almost 2.5 years, when implanted in the monkey abdomen, and a pig life-supporting kidney could also function for over 1.3 years in monkeys. Concerning islets, islets from gene-editing pigs could work for more than one year in monkeys. It is noteworthy that one group reported a survival of adult wild-type pig islets of over 600 days. On the other hand, the progress in these preclinical trials strongly affected not only the xenotransplantation study itself but regeneration studies to use pigs as a scaffold to foster human induced pluripotent stem cells

USSR Space Life Sciences Digest, issue 31

This is the thirty first issue of NASA's Space Life Sciences Digest. It contains abstracts of 55 journal papers or book chapters published in Russian and of 5 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 18 areas of space biology and medicine. These areas include: adaptation, biological rhythms, cardiovascular and respiratory systems, endocrinology, enzymology, genetics, group dynamics, habitability and environmental effects, hematology, life support systems, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, operational medicine, psychology, radiobiology, and space biology and medicine

3D Cell Printed Tissue Analogues: A New Platform for Theranostics

Stem cell theranostics has received much attention for noninvasively monitoring and tracing transplanted therapeutic stem cells through imaging agents and imaging modalities. Despite the excellent regenerative capability of stem cells, their efficacy has been limited due to low cellular retention, low survival rate, and low engraftment after implantation. Three-dimensional (3D) cell printing provides stem cells with the similar architecture and microenvironment of the native tissue and facilitates the generation of a 3D tissue-like construct that exhibits remarkable regenerative capacity and functionality as well as enhanced cell viability. Thus, 3D cell printing can overcome the current concerns of stem cell therapy by delivering the 3D construct to the damaged site. Despite the advantages of 3D cell printing, the in vivo and in vitro tracking and monitoring of the performance of 3D cell printed tissue in a noninvasive and real-time manner have not been thoroughly studied. In this review, we explore the recent progress in 3D cell technology and its applications. Finally, we investigate their potential limitations and suggest future perspectives on 3D cell printing and stem cell theranostics.116Nsciescopu