We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
Background
Apical papilla stem cells (SCAPs) exhibit significant potential for tissue repair, characterized by their anti-inflammatory and pro-angiogenic properties. Exosomes derived from stem cells have emerged as safer alternatives that retain comparable physiological functions. This study explores the therapeutic potential of exosomes sourced from SCAPs in the treatment of non-alcoholic steatohepatitis (NASH).
Methods
A NASH mouse model was established through the administration of a high-fat diet (HFD), and SCAPs were subsequently isolated for experimental purposes. A cell model of NASH was established in vitro by treating hepatocellular carcinoma cells with oleic acid (OA) and palmitic acid (PA). Exosomes were isolated via differential centrifugation. The mice were treated with exosomes injected into the tail vein, and the hepatocytes were incubated with exosomes in vitro. After the experiment, physiological and biochemical markers were analyzed to assess the effects of exosomes derived from SCAPs on the progression of NASH in both NASH mouse models and NASH cell models.
Results
After exosomes treatment, the weight gain and liver damage induced by HFD were significantly reduced. Additionally, hepatic fat accumulation was markedly alleviated. Mechanistically, exosomes treatment promoted the expression of genes involved in hepatic fatty acid oxidation and transport, while simultaneously suppressing genes associated with fatty acid synthesis. Furthermore, the levels of serum inflammatory cytokines and the mRNA expression of inflammatory markers in liver tissue were significantly decreased. In vitro cell experiments produced similar results.
Stem Cell-Derived Exosomes: Natural Intercellular Messengers with Versatile Mechanisms for the Treatment of Diabetic Retinopathy
Diabetic retinopathy is one of the complications of diabetes mellitus that occurs in the early stages. It is a disease that has a serious impact, and may lead to blindness when the disease progresses to advanced stages. Currently, treatments for diabetic retinopathy are mainly limited to its advanced stages of the disease, being restricted to a single therapeutic mechanism. Stem cells hold the promise of regenerative therapy and have the potential to comprehensively improve diabetic retinopathy. However, direct stem cell therapy carries some risk of carcinogenesis. Exosomes secreted by stem cells have shown a similar overall improvement in disease as stem cells. Exosomes can carry a number of biologically active materials from donor cells to recipient cells or distant organs, regulating intercellular signaling. Exosomes have shown remarkable efficacy in alleviating oxidative stress, inhibiting inflammatory responses, suppressing angiogenesis, reducing apoptosis and protecting neural tissues. Currently, the experimental literature using stem cell exosomes in the treatment of diabetic retinopathy tends to converge on the above experimental results. With this in mind, we have chosen to explore exosomes in depth from a subtle molecular perspective. We will elaborate on this perspective in this paper and propose to advocate exosome therapy as one promising approach for the treatment of diabetic retinopathy to ameliorate the lesions through multiple mechanisms.
Exosomes, peptides and peri-procedure management – comparative investigations
Introduction: Exosome technology is a promising new advancement in therapeutic options but is still in its early stages, leading to uncertainties. A small pilot study compared traditional peptide technology (Regenerating Skin Nectar with TriHex Technology® and TriHex Technology® peptide + Octapeptide) to two leading exosome products (Stem cell derived Lyophilized exosomes and Platelet derived exosomes) for post-procedure use. These studies were carried out on pre-clinical (ex vivo) and clinical front to investigate effects on the extracellular matrix, dermo-epidermal junction, and skin tolerance as post-procedure outcomes.
Methods and materials: The ex vivo model study was conducted by 3D Genomics using photodamaged skin from facelift patients. The skin was divided, processed under BSL2 conditions and cultured in transwells with specific media. Treatments, including peptides and platelet-derived products, were applied daily for 7 days, while stem cell-derived exosomes were applied as a single application as per the described usage. One set was left untreated as a control.
Skin samples were treated and analyzed using immunohistochemistry staining for tropoelastin and CD44. RNA was isolated after treatments and sequenced to assess changes in gene expression. The study aimed to compare the effects of different treatments on skin regeneration and tolerance. Clinically, the participants underwent microneedling of the face and applied exosomes and peptides on each side of the face as comparisons. Participants completed questionnaires on Day 0. On Days 0,1,2,3 and 4 participants completed their self-healing ratings and were also assessed by an assessor on their healing rating on a 5-point scale.
Results: The plated exosome products exhibited significant toxicity in the ex vivo model and neither of the exosome products produced relevant changes in gene expression or regenerative effects in this model. Participants in the small clinical series experienced unpleasant burning and stinging in keeping with the effects seen in the ex vivo model. In contrast, the peptide technology showed favorable gene expression upregulation and histological changes in the extracellular matrix and was well-tolerated and comfortable for post-procedure use, as has been demonstrated in multiple clinical trials.
Conclusion: The overall impression from these pilot studies suggests that peptide formulations are better tolerated and more effectively target ECM regenerative effects. Conversely, exosome preparations appear to be prone to skin reactions and lack clear targeting of skin regenerative pathways.