Aabstract

Exposure to a space environment characterized by the absence of mechanical loading significantly reduces both the differentiation and the regenerative potential of embryonic stem cells. In a study conducted aboard a space shuttle during the Discovery mission, murine embryonic stem cells were cultured in embryoid bodies for fifteen days under microgravity conditions. These embryoid bodies were compared with those maintained under terrestrial gravitational conditions. The results revealed that, in the absence of the usual mechanical stimulation, the embryoid bodies exhibited a marked inhibition in the expression of markers associated with terminal differentiation, while retaining elevated levels of self-renewal. This finding indicates that the cells remain in an immature state, which may be interpreted as a preservation of regenerative potential, yet simultaneously poses a significant challenge for tissue repair during long-duration spaceflights. Gene expression analysis further revealed alterations in signaling pathways essential for cellular maturation, including those related to Notch and Wnt. Additionally, a reduced consumption of glucose was observed, suggesting decreased metabolic activity within the space environment. Interestingly, upon return to terrestrial gravitational conditions, the embryoid bodies previously exposed to microgravity demonstrated an increased potential to differentiate into colonies of specialized cardiac muscle cells. These findings underscore the critical role of mechanical loading in promoting normal cellular differentiation and tissue regeneration. They also highlight the necessity of developing countermeasures that simulate mechanical stimulation to ensure proper tissue repair during extended space missions.

Abstract

Liver diseases have become a major global health burden that comprises of broad spectrum of diseases with multiple causes. Their diagnosis and treatment have progressed greatly over the years however their clinical outcomes are still not satisfying. Most liver diseases progress to end-stage liver disease (ESLD), which is characterised by large amounts of matrix deposition that makes it difficult for the liver and its hepatocytes to regenerate. In this scenario, Liver transplantation was the only treatment for the end-stage liver disease. Moreover, the shortage of suitable organs, expensive treatment costs and surgical complications greatly reduced the patient’s survival rates. So, need for an effective treatment modality has become imperative. Cell therapy has become the research hotspot in the field of regenerative medicine. Among the various types of stem cells such as Embryonic stem cells (ESCs), Mesenchymal Stem Cells (MSCs), and Induced pluripotent stem cells (iPSCs), MSCs play an important role in the field of regenerative medicine due to several properties such as paracrine function, immunomodulatory properties, immune suppressive properties, ability to home at the site of injury etc. Exosomes derived from Mesenchymal stem cell (MSC) have been reported to play important roles in physiological or biological processes in acute or chronic liver disorders by horizontal transferring of genetic bio information from donor cells to neighboring or distal target cells.

The Research work  specializes in Isolation, expansion, characterization and differentiation of human Mesenchymal Stem Cells and Hepatic Progenitor cells. As an initiative towards producing clinical grade stem cells, several human based supplements for culture of stem cells have been optimised as an alternative for animal based serum. Pre-clinical studies on animal models have also been pursued. The results of the work undertaken will be presented

Abstract

Using 5-8 Kg young macaque monkeys after transient global brain ischemia, we studied both neuronal death in the hippocampal CA1 and adult neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG). As a mechanism of CA1 neuronal death, we formulated the ‘calpain-cathepsin hypothesis’. Here, ‘polyunsaturated fatty acid (PUFA) – G-protein coupled receptor 40 (GPR40) – cAMP response element-binding protein (CREB) – brain-derived neurotrophic factor (BDNF)’ signalling, is discussed as a regulator of adult neurogenesis specific for primates. Transient brain ischemia induced an increase of the neuronal progenitor cells in SGZ maximally in the 2nd week. To identify the origin and nature of SGZ progenitor cells, we compared DG tissues before and after ischemia by differential display, and DG versus CA1 by Western blotting, laser confocal, and electron microscopic analyses. Immunofluorescence microscopy showed that 1–3% of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the SGZ were also positive for neuronal markers such as TUC4, βIII tubulin, and NeuN, or glial markers such as Iba1 or S-100β on days 9 and 15. In contrast, despite the presence of numerous BrdU-positive cells, CA1 showed no neurogenesis, and the progenitors were positive only for Iba1 or S-100β on days 4, 9, and 15. The vascular adventitia of the SGZ was a source of as newborn neurons, astrocytes, and microglia (Top Left). Among 14 genes upregulated on differential display, we focused on Down syndrome cell adhesion molecule (DSCAM) known to play a crucial role during neuronal development, and characterized its expression pattern and that of polysialylated neural cell adhesion molecule (PSA-NCAM). DSCAM upregulation after ischemia was obderved in three cell types: immature neurons positive for PSA-NCAM, mature DG neurons, and newborn astrocytes positive for S100β. Young astrocytes positive for BDNF were in intimate contact with PSA-NCAM-positive neurons in SGZ. Expressions of GPR40, pCREB, BDNF, and DSCAM were upregulated in the SGZ immature neurons at the 2nd week on immunoblotting and/or immunohistochemistry. Presumably, PSA-NCAM contributes to building networks among newborn neurons, while DSCAM to networks with pre-existing neurons.

Abstract

Adipose-derived stem cells (ADSCs) have emerged as a valuable cell source in regenerative medicine due to their multipotency and accessibility. This study explores the potential of photobiomodulation (PBM) to enhance neuronal differentiation of ADSCs and address limitations in conventional in vitro models. PBM has been shown to promote neuronal-like trans-differentiation by modulating key signaling pathways and facilitating the formation of neural embryoid bodies. These effects suggest a pivotal role for PBM in directing lineage-specific differentiation toward functional neuronal phenotypes. The integration of PBM into three-dimensional culture systems further simulates the native microenvironment, improving differentiation efficiency and cellular organization. These findings highlight the potential of PBM as a non-invasive and effective tool in developing ADSC-based strategies for neuro-regenerative therapies, offering new avenues in personalized medicine and brain tissue engineering.