Vol 19, No 6 (2024)

Acute radiation syndrome (ARS) is also known as triple syndrome, which develops after whole-body radiation exposure. During unforeseen exposures, these syndromes are set in depending on the dose of radiation. Cell-based therapy, especially using stem cells and their soluble factors, is gaining wide attention in the field of regenerative medicine to treat various diseases, including degenerative diseases. Stem cells attract prime attention because of their profound inherent tissue repair capability and regeneration potential. Further, stem cell therapy can be one of the promising strategies for the amelioration of ARS because of its ability to lodge in damaged tissue and release regenerative cytokines by sensing the local injury. In this regard, human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) have gained substantial attention for their applications in the treatment of various human diseases due to several advantages offered by them. This article is intended to provide future perspective on the use of WJ-MSCs for the management of accidental radiation injury in pre-clinical models, and finally, their utility in regeneration of damaged tissues and organs.

Intervertebral disc degeneration (IVDD) is a serious condition that manifests as low back pain, intervertebral disc protrusion, and spinal canal stenosis. At present, the main treatment methods for IVDD are surgical interventions such as discectomy, total disc replacement, and spinal fusion. However, these interventions have shown limitations, such as recurrent lumbar disc herniation after discectomy, lesions in adjacent segments, and failure of fixation. To overcome these shortcomings, researchers have been exploring stem cell transplantation therapy, such as mesenchymal stem cell (MSC) transplantation, but the treatment results are still controversial. Therefore, researchers are in search of new methods that are more efficient and have better outcomes. The exosomes from stem cells contain a variety of bioactive molecules that mediate cell interactions, and these components have been investigated for their potential therapeutic role in the repair of various tissue injuries. Recent studies have shown that MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on nucleus pulposus cells, annulus fibrosus, and cartilage endplate. miRNAs play a role in many cell activities, such as cell proliferation, apoptosis, and cytokine release, by acting on mRNA translation, and they may have immense therapeutic potential, especially when combined with stem cell therapy. This article reviews the current status of research on intervertebral disc repair, especially with regard to the latest research findings on the molecular biological mechanisms of miRNAs in MSC-derived exosomes in intervertebral disc repair.

Stem cells, which were initially identified in the 1900s, are distinct cells with the potential to replenish themselves as well as differentiate into specialised cells with certain forms and functions. Cancer stem cells play a significant role in the growth and recurrence of the tumours and, similar to normal stem cells, are capable of proliferating and differentiating. Traditional cancer treatments are ineffective against cancer stem cells, which leads to tumour regrowth. Cancer stem cells are thought to emerge as a result of epithelial-to-mesenchymal transition pathways. Brain, prostate, pancreatic, blood, ovarian, lung, liver, melanomas, AML, and breast cancer stem cells are among the most prevalent cancer forms. This review aims to comprehend the possibility of using specific forms of nanotechnology to replace cancer stem cells. In terms of nanotechnology, magnetic nanoparticles can deliver medications, especially to the target region without harming healthy cells, and they are biocompatible. In order to kill glioma cancer stem cells, the gold nanoparticles bond with DNA and function as radio sensitizers. In contrast, liposomes can circulate and traverse biological membranes and exhibit high therapeutic efficacy, precise targeting, and better drug release. Similar to carbon nanotubes, grapheme, and grapheme oxide, these substances can be delivered specifically when utilized in photothermal therapy. Recent treatments including signaling pathways and indicators targeted by nanoparticles are being researched. Future research in nanotechnology aims to develop more effective and targeted medicinal approaches. The results of the current investigation also showed that this technology's utilization will improve medical therapy and treatment.

Tissue engineering and regenerative medicine have received significant attention in treating degenerative disorders and presented unique opportunities for researchers. The latest research on tissue engineering and regenerative medicine to reconstruct the alveolar cleft has been reviewed in this study. Three approaches have been used to reconstruct alveolar cleft: Studies that used only stem cells or biomaterials and studies that reconstructed alveolar defects by tissue engineering using a combination of stem cells and biomaterials. Stem cells, biomaterials, and tissue-engineered constructs have shown promising results in the reconstruction of alveolar defects. However, some contrary issues, including stem cell durability and scaffold stability, were also observed. It seems that more prospective and comprehensive studies should be conducted to fully clarify the exact dimensions of the stem cells and tissue engineering reconstruction method in the therapy of alveolar cleft.

Bone tissue is composed of organic minerals and cells. It has the capacity to heal for certain minor damages, but when the bone defects surpass the critical threshold, they need fixing. Bone regeneration through natural and synthetic biodegradable materials requires various steps, such as manufacturing methods and materials selection. A successful biodegradable bone graft should have a high surface area/ volume ratio, strength, and a biocompatible, porous structure capable of promoting cell adhesion, proliferation, and differentiation. Considering these requirements, the electrospinning technique is promising for creating functional nano-sized scaffolds. The multi-axial methods, such as coaxial and triaxial electrospinning, are the most popular techniques to produce double or tri-layered scaffolds, respectively. Recently, stem cell culture on scaffolds and the application of osteogenic differentiation protocols on these scaffolds have opened new possibilities in the field of biomaterials research. This review discusses an overview of the progress in coaxial and triaxial technology through biodegradable composite bone materials. The review also carefully elaborates the osteogenic differentiation using stem cells and their performance with nano-sized scaffolds.

Mesenchymal stem/stromal cells (MSCs) have exhibited potential for treating multiple inflammation- related diseases (IRDs) due to their easy acquisition, unique immunomodulatory and tissue repair properties, and immune-privileged characteristics. It is worth mentioning that MSCs release a wide array of soluble bioactive components in the secretome that modulate host innate and adaptive immune responses and promote the resolution of inflammation. As the first line of defense, macrophages exist throughout the entire inflammation process. They continuously switch their molecular phenotypes accompanied by complementary functional regulation ranging from classically activated pro-inflammatory M1-type (M1) to alternatively activated anti-inflammatory M2-type macrophages (M2). Recent studies have shown that the active intercommunication between MSCs and macrophages is indispensable for the immunomodulatory and regenerative behavior of MSCs in pharmacological cell therapy products. In this review, we systematically summarized the emerging capacities and detailed the molecular mechanisms of the MSC-derived secretome (MSC-SE) in immunomodulating macrophage polarization and preventing excessive inflammation, providing novel insights into the clinical applications of MSC-based therapy in IRD management.

Background::Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD.

Objectives::To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process.

Method::ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) from postnatal day 0 (P0) to P7, and returned to room air until P14 to mimic BPD. ADSC-Exos was treated by intratracheal or intravenous administration on P4. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters.

Results::Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration

Conclusion::The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.