Cell Transplantation最新文献

The lung is a vital organ in the respiratory system, and there is a critical need to develop more effective methods for lung health management. Extracellular vesicles (EVs) play an important role in intercellular communication. They exhibit high bioavailability and low immunogenicity, making them essential in maintaining cellular homeostasis and in the prevention and treatment of numerous diseases. This review describes the diverse sources, isolation techniques, functions, and challenges associated with EVs, particularly exosomes. We highlight their significant role in the diagnosis and treatment of lung diseases, as well as their potential as drug delivery vehicles. By synthesizing recent advances in EVs research, this review aims to provide a theoretical foundation for future studies and clinical applications of EVs.

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine from the urethra due to increased abdominal pressure. The complex pathophysiological mechanisms underlying SUI have driven the development of diverse therapeutic strategies. Current treatment options encompass both conservative and surgical interventions, with surgical approaches generally often regarded as the most effective option approach for severe cases. However, many surgical techniques carry significant risks of complications. In this context, urethral injection therapy, primarily based on stem cell-mediated regenerative approaches, has emerged as a minimally invasive alternative. Stem cell therapies leverage their multipotent differentiation capacity and paracrine signaling pathways to directly target the pathophysiological contributors to SUI, including urethral sphincter dysfunction, neuromuscular junction degeneration, and imbalances in elastin and collagen homeostasis. This narrative review provides a critical evaluation of current stem cell-mediated regenerative strategies for SUI, focusing on cellular mechanisms and the therapeutic effects driven by paracrine signaling. Recent clinical advances, unresolved scientific controversies, and innovative combinatorial delivery systems incorporating targeted therapeutic approaches are analyzed. Despite challenges remain, such as determining the optimal stem cell dosage and improving in vivo survival rates, ongoing research offers valuable insights into the development of cell-free bioactive derivatives, advanced combination delivery systems, and precise molecularly targeted therapies.

This study presents an examination of whether the double overexpression of ZNF746 and cellular prion protein (PrP^C) genes in rat adipose-derived mesenchymal stromal cells (ADMSCs) (ie, MSC^DGe-OVE) offered enhanced protection to the livers of rats against ischemia‒reperfusion (IR) injury. The in vitro results revealed that compared with those of rat ADMSCs, cell activities (viability/proliferation/growth/cell cycle process) were significantly upregulated by the overexpression of either gene in rat ADMSCs and were further significantly increased by MSC^DGe-OVE, whereas the expression of biomarkers of oxidative stress/ROS/apoptosis/fibrosis/autophagy decreased with increasing cell viability among the groups (all P < 0.001). Male adult SD rats (n = 50) were equally categorized into groups 1 (sham-operated-control), 2 (IR), 3 (IR-MSC^OVE-PrPC), 4 (IR-MSC^{OVE- ZNF746}), and 5 (IR-MSC^DGe-OVE), and livers were harvested by day 3. By day 3, the number of circulatory inflammatory/immune cells, protein expression of oxidative stress/apoptotic/fibrotic/mitochondrial damage/autophagic biomarkers, and cellular levels of DNA damage/fibrosis/inflammation in the liver parenchyma were lowest in group 1, highest in group 2 and significantly lower in groups 3/4 than in group 5 (all P < 0.0001). Liver fibrosis detected by ultrasound and the liver injury score displayed identical patterns of circulatory levels of immune cells among the groups (all P < 0.0001). Upstream and downstream inflammatory and cell-stress signaling pathways were identified as playing crucial roles in acute liver IR injury. In conclusion, MSC^DGe-OVE enhanced cell proliferation and growth and ameliorated IR-induced liver damage.

Type 1 diabetes remains an incurable autoimmune disease, and despite advances in insulin-delivery systems, many patients still face severe hypoglycemia, glucose variability, and psychological burden. Beta-cell replacement offers a transformative alternative, with allogeneic islet transplantation providing durable protection and improved quality of life, yet limited by donor availability and the need for immunosuppression. Stem cell-derived islet-like clusters are now reaching clinical milestones, showing promising insulin independence and glycemic control, while encapsulation, autologous induced pluripotent stem cells (iPSC)-derived therapies, and gene-edited "hypo-immune" cells aim to overcome immune barriers. Porcine islet xenotransplantation is also being revisited, although regulatory and immunological hurdles remain. Key challenges persist in cell delivery, engraftment, and long-term function. As cell therapy transitions from experimental proof-of-concept to clinical reality, success will require scalable manufacturing, safe and effective delivery, regulatory alignment, and patient-centered approaches to ensure broad and meaningful impact.

Pancreatic islet transplantation is an effective therapy for type 1 diabetes; however, its broader clinical application is limited by the shortage of donors. Establishing long-term culture methods for isolated islets is an area of ongoing investigation that may ultimately support applications such as biobanking and stem cell-derived islets. However, maintaining transplantable quality of islets during extended culture remains a challenge. We recently developed a method for human islet culture on optimally sized microwells that preserves viability over two weeks. Despite improved viability, other key pre-transplantation factors, such as islet metabolism, remained reduced, indicating a need for further optimization. To identify potential targets for improvement, we performed RNA sequencing on human islets from three deceased donors, comparing two-week cultures (microwell and conventional) versus pre-culture controls. Transcriptomic analysis showed significant gene expression changes in two-week-cultured islets compared to pre-culture islets, whereas microwell and conventional culture conditions showed minimal differences despite improved viability in microwell culture. Pathway analysis revealed that long-term culture consistently downregulates heavy metal ion-related pathways, particularly zinc-related pathways regulated by metallothioneins. This suggests a loss of β-cell characteristics during extended culture. Our findings highlight intra-islet metal ion homeostasis as a potential therapeutic target for improving transplantation outcomes following prolonged islet culture.

Hepatocyte transplantation (HTx) is a promising alternative to liver transplantation; however, poor engraftment remains a major challenge. Although co-transplantation with adipose tissue-derived stromal cells (ADSCs) or islets improves engraftment, exposure of these cells to the portal vein enhances innate immune responses, resulting in a significant loss of hepatocytes. Therefore, we investigated HTx at the liver surface as a novel approach that does not involve the portal vein. Hepatocytes were transplanted onto the liver surface of syngeneic analbuminemic rats with or without ADSCs and/or islets. Serum albumin levels and immunohistochemical staining of the transplanted hepatocytes were evaluated. Hepatocyte engraftment was compared between the liver surface and intraportal groups. To examine the detailed mechanisms behind co-transplantation, co-cultured supernatants were analyzed using multiplex assays, and inhibition tests using neutralizing antibodies were performed. Results showed that islet and ADSC co-transplantation markedly enhanced hepatocyte engraftment at the liver surface (P < 0.01), and its efficiency was comparable to that of intraportal transplantation (P = 0.35). In the co-transplantation group, cells were not necessarily in proximity, suggesting that humoral factors are important. In an in vitro study, hepatocyte function was significantly improved by co-culturing with islets and ADSCs (P < 0.01). Multiplex assays and inhibition tests revealed several important humoral factors, most notably insulin, which promoted hepatocyte engraftment. These findings suggest that HTx at the liver surface, together with crucial factors, may be a novel alternative strategy for intraportal transplantation.

The mechanisms underlying scarless versus fibrotic wound healing remain a critical challenge in regenerative medicine. To elucidate the mechanisms of scarless repair, the axolotl (Ambystoma mexicanum), a model organism with exceptional regenerative capacity, has gained increasing prominence. Although axolotls are capable of regenerating complex structures such as limbs and tails, whether their skin regeneration is uniformly scarless-especially across different anatomical sites-remains undefined. Here, we demonstrate that adult axolotl tail skin achieves scarless regeneration, while dorsal skin repair results in fibrotic scarring. Through comparative histological and transcriptomic analyses of full-thickness excisional wounds, we identify accelerated re-epithelialization and reduced collagen deposition in tail skin compared to dorsal wounds. Developmental trajectory studies reveal prolonged retention of a hypodifferentiated state in tail skin, contrasting with early stratification in dorsal tissue. Mechanistically, we find that the extracellular matrix (ECM) glycoprotein gene Tenascin-N (TnN) exhibits higher expression in tail skin versus dorsal skin. The reported TnN downstream PI3K-Akt signaling pathway, demonstrated by Western blotting of pAkt, is significantly activated in tail skin versus dorsal skin during homeostasis and regeneration. These findings establish the axolotl as a key model for dissecting how developmental priming and ECM dynamics orchestrate regenerative versus fibrotic repair, offering novel insights for therapeutic strategies targeting scarless healing.

Allogeneic islet transplantation becomes a viable option for patients with unstable type 1 diabetes. However, considering the huge number of patients with type 1 diabetes, human donor shortage is a serious issue. To overcome the donor shortage issue, xenotransplantation is an attractive option. In fact, clinical islet xenotransplantation has been conducted since 1990s. The first clinical trial was performed using fetal pigs and demonstrated the porcine pancreatic tissue could survive in human body with immunosuppressive strategies. To scale up the islet production, Canadian group established a method for islet isolation from neonatal pigs. Their method has been used for clinical islet xenotransplantation in New Zealand, Russian, Mexico, Argentina, and China. Recently Korean group published a clinical protocol for islet xenotransplantation using adult pigs. For the next generation of islet xenotransplantation, gene-modified pigs were created. Especially "superislets" created by Belgian group demonstrated promising preclinical outcomes. With advanced donor pigs, islet xenotransplantation might become a suitable treatment for the majority of type 1 diabetic patients.

Non-cryo and hypothermic preservations are two available options for short-term storage of living cells. For long-term cell storage, cryopreservation is an essential procedure as it prolongs the storage time, allowing for the transport and testing of cells, as well as the establishment of cell banks. But it is unclear whether cryopreservation reduces the therapeutic effects of human umbilical cord mesenchymal stem cells (hucMSCs) on osteoarthritis (OA). To investigate this, we compared the basic biological characteristics and the anti-OA efficacy of un-cryopreserved hucMSCs (UC-MSCs) and cryopreserved hucMSCs (C-MSCs). A mono-iodoacetate-induced rat OA model was established to evaluate the anti-OA properties of UC-MSCs and C-MSCs. And the conditioned medium of UC-MSCs (UC-CM) and cell freezing medium of C-MSCs (C-CFM) were collected for the mechanism study. No significant differences were found between UC-MSCs and C-MSCs in cell viability, immunophenotype, and trilineage differentiation capacity. In vivo, UC-MSCs and C-MSCs exhibited similar cartilage-repairing effects by attenuating pain and alleviating pathological changes in OA rat joints. In vitro, C-CFM and UC-CM promoted the proliferation of chondrocytes, improved the expression of anabolism-related molecules (Col2, COL2, and SOX9), and decreased the expression of catabolism-related molecules (Adamts5, Mmp13, Il6, COL10, and MMP13). These results indicated that UC-MSCs and C-MSCs had comparable anti-OA effects, and cryopreservation did not alter the anti-OA capability of hucMSCs, which provides further support for clinical use of C-MSCs in treating OA.

The differentiation of adipose-derived stem cells (ADSCs) into tendon cells is a key process in tissue engineering and regenerative medicine. The Wnt signaling pathway plays a key role in regulating cell fate and tissue-regeneration decisions, making it a promising target for improving tendon differentiation. Photobiomodulation (PBM) is a non-invasive therapeutic approach that has been shown to modulate cellular processes, including stem cell differentiation. The aim of this review is to provide an understanding of the effects of PBM and Wnt signaling on ADSC differentiation. The complexities of interactions between PBM and dynamic Wnt pathway exist in different ways during the differentiation of ADSCs into tendon cells. The results highlight the potential therapeutic application of PBM in promoting tendon healing and regeneration. This review explores the clinical importance of PBM-mediated Wnt signaling regulation in tendon injuries. The results of this review will provide valuable information for the rational design of therapeutic strategies to enhance tendon differentiation and improve clinical outcomes and will also contribute to increasing knowledge of the synergistic relationship between PBMs, Wnt signaling pathways, and stem cell differentiation.