BACKGROUND: Facilitating the healing process of injured anterior cruciate ligament (ACL) tissue is crucial for patients to safely return to sports. Stem cell derived exosomes have shown positive effects on enhancing the regeneration of injured tendons/ligaments. However, clinical application of exosomes in terms of storage and pre-assembly is challenging. We hypothesized that lyophilized exosomes derived from human umbilical cord stem cells (hUSC-EX) could enhance the cell activity of chronically injured ACL cells.
METHODS: We harvested the 8 weeks injured ACL cells from rabbit under IACUC (No. 110232) approval. The studied exosomes were purified from the culture medium of human umbilical cord stem cells (IRB approval No. A202205014), lyophilized to store, and hydrated for use. We compared exosome treated cells with non-exosome treated cells (control group) from the same rabbits. We examined the cell viability, proliferation, migration capability and gene expression of type I and III collagen, TGFβ, VEGF, and tenogenesis in the 8 weeks injured ACL cells after hUSC-EX treatment.
RESULTS: After hydration, the average size of hUSC-EX was 84.5 ± 70.6 nm, and the cells tested positive for the Alix, TSG101, CD9, CD63, and CD81 proteins but negative for the α-Tubulin protein. After 24 h of treatment, hUSC-EX significantly improved the cell viability, proliferation and migration capability of 8 weeks injured ACL cells compared to that of no exosome treatment group. In addition, the expression of collagen synthesis, TGFβ, VEGF, and tenogenesis gene were all significantly increased in the 8 weeks injured ACL cells after 24 h hUSC-EX delivery.
CONCLUSIONS: Lyophilized exosomes are easily stored and readily usable after hydration, thereby preserving their characteristic properties. Treatment with lyophilized hUSC-EX improved the activity and gene expression of 8 weeks injured ACL cells.
CONCLUSIONS: Lyophilized hUSC-EX preserve the characteristics of exosomes and can improve chronically injured (8 weeks) ACL cells. Lyophilized hUSC-EX could serve as effective and safe biomaterials that are ready to use at room temperature to enhance cell activity in patients with partial ACL tears and after remnant preservation ACL reconstruction.

UNASSIGNED: Mesenchymal stem cells (MSCs) play a key role in regenerative medicine due to their capacity to differentiate into multiple cell lines, regulate the immune system, and exert paracrine effects. The therapeutic impact of MSCs is primarily mediated through their secretome. The secretory and therapeutic potential of MSCs can be improved through preconditioning, which entails the application of hypoxic environments, 3-dimensional cell cultures, and pharmacological agents. Valproic acid (VPA) is a histone deacetylase inhibitor that is employed in medical practice for treating epilepsy and bipolar disorder. Hence, preconditioning MSCs with VPA is expected to induce histone acetylation, enhance gene expression, and beneficially modify the cells\' secretomes.
UNASSIGNED: To assess the effectiveness of VPA in enhancing and regulating the therapeutic potential of cells as well as its impact on MSC secretome profiles and ultrastructural morphologies.
UNASSIGNED: Expiremental study.
UNASSIGNED: Human umbilical cord MSCs were preconditioned with 2 mM VPA for 24 and 48 hours; untreated MSCs served as controls. The secretome secreted by the cells was assessed for its total protein content. Subsequently, interferon-gamma (IFN-γ), interleukin-17 (IL-17), IL-10, vascular endothelial growth factor, nerve growth factor (NGF), glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor (BDNF) levels in the secretome were analyzed using the ELISA method. The ultrastructural properties of the cells were studied under transmission electron microscopy.
UNASSIGNED: Ultrastructural examinations revealed that the chromatin content of VPA-treated cells was reduced. VPA-preconditioned cells exhibited a higher density of rough endoplasmic reticulum, autophagic vesicles, and myelin figures on cytoplasmic structure analysis, which was indicative of increased secretion. Protein secretion was elevated in those cells, with notable increases in NGF and BDNF levels. Furthermore, the cytoskeletal rearrangement and elevated autophagic activity observed in the 48-hour preconditioned cells could indicate the initiation of neuronal differentiation. IL-10, IL-17, and IFN-γ were not detected in the secretome.
UNASSIGNED: This study indicate that preconditioning with VPA enhances MSC activity and subsequently modifies the secretome content.

UNASSIGNED: Congenital hernia of the umbilical cord (CHUC) is the rarest type of anterior abdominal wall defect, in which an intact umbilical ring is always present and viscera pass through the base of normal-looking umbilicus.
UNASSIGNED: This study was conducted to document the intraoperative findings and postoperative outcomes of patients with congenital hernia of the umbilical cord up to discharge from a tertiary care center.
UNASSIGNED: This study was a retrospective observational study conducted for two years (August 2020 to July 2022) in the Department of Pediatric Surgery, at the tertiary health care center of UP, India.
UNASSIGNED: During this two-year duration, a total of 10 cases with CHUC were seen in our department and were surgically managed. In this study, out of these 10 patients (male 7 and female 3), eight had normal gastrointestinal tract, one had accessory liver tissue on thin pedicle, and one had features of gangrenous bowel. Of these 10 cases, three patients developed postsurgical complications in which two patients developed superficial wound infection while one developed wound dehiscence. No mortality was noted.
UNASSIGNED: Congenital hernia of the umbilical cord induces stress on parents and relatives. In this study, we conclude that the majority of cases had normal gastrointestinal tract and had no serious postoperative complications up to discharge.

BACKGROUND: Despite advancements in reconstructive procedures, ischemia-reperfusion (I/R) injury remains a significant challenge in reconstructive surgery, with mitochondrial dysfunction playing a pivotal role. Mitochondrial transplantation has emerged as a promising therapeutic strategy to address this issue. This study aims to evaluate the impact of umbilical cord mesenchymal stem cell-derived mitochondrial transplantation on skin flap I/R models in rats.
METHODS: Twenty male rats underwent I/R injury on skin flaps, with or without mitochondrial transplantation administered via intravenous or subcutaneous routes. Analysis encompassed histopathology, inflammatory, apoptotic, oxidative stress, and hypoxia markers.
RESULTS: Results revealed a reduction in inflammation, apoptosis, oxidative stress, and hypoxia in the transplantation group compared to controls.
CONCLUSIONS: The findings suggest that umbilical cord mesenchymal stem cell-derived mitochondrial transplantation shows promise in enhancing flap viability and attenuating I/R injury, offering valuable insights for improved outcomes in reconstructive surgery. However, further exploration in larger animal models and refinement of delivery methods and dosage are warranted to fully elucidate its clinical translatability.

BACKGROUND: Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms.
METHODS: This prospective, self-controlled clinical study was conducted at Henan Provincial People\'s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation.
RESULTS: Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy.
CONCLUSIONS: UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines.
BACKGROUND: The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

The heavy chain (HC)-hyaluronan (HA)/pentraxin 3 (HC-HA/PTX3) complex is formed by tumor necrosis factor-stimulated gene-6 (TSG-6) catalyzing the covalent (ester bond) transfer of HC1 from inter-α-trypsin inhibitor (IαI) to HA followed by tight binding of PTX3. The presence of such a complex has been found in human amniotic membrane (AM) and is considered to be a major matrix component responsible for its anti‑inflammatory and anti‑scarring properties to promote regenerative healing. Because the therapeutic potentials of AM and umbilical cord (UC) are similar, we herein evaluated whether human UC also contains HC-HA/PTX3. Immunostaining of UC cross-sections showed abundant PTX3, HC1, HA, TSG-6, and bikunin. Western blot analysis suggested the presence of HC1 complex bound via a NaOH-sensitive bond and tightly bound to PTX3 multimer in UC and AM extracts but not in chorion and placenta extracts. HC-HA/PTX3 was purified from UC extract by successive runs of density gradient ultracentrifugation and verified the presence of HC1 but not HC2 or HC3 based on western blot analysis. These results suggest the presence of HC-HA/PTX3 complex in UC is similar to AM.

BACKGROUND: Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications.
METHODS: Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide.
RESULTS: Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton\'s jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days.
CONCLUSIONS: Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use.

UNASSIGNED: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.
UNASSIGNED: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).
UNASSIGNED: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.
UNASSIGNED: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

Although therapies based on mesenchymal stromal cells (MSCs) are being implemented in clinical settings, many aspects regarding these procedures require further optimization. Domestic dogs suffer from numerous immune-mediated diseases similar to those found in humans. This study aimed to assess the immunomodulatory activity of canine (c) Wharton jelly (WJ)-derived MSCs and refer them to human (h) MSCs isolated from the same tissue. Canine MSC(WJ)s appeared to be more prone to in vitro aging than their human counterparts. Both canine and human MSC(WJ)s significantly inhibited the activation as well as proliferation of CD4+ and CD8+ T cells. The treatment with IFNγ significantly upregulated indoleamine-2,3-dioxygenase 1 (IDO1) synthesis in human and canine MSC(WJ)s, and the addition of poly(I:C), TLR3 ligand, synergized this effect in cells from both species. Unstimulated human and canine MSC(WJ)s released TGFβ at the same level (p > 0.05). IFNγ significantly increased the secretion of TGFβ in cells from both species (p < 0.05); however, this response was significantly stronger in human cells than in canine cells. Although the properties of canine and human MSC(WJ)s differ in detail, cells from both species inhibit the proliferation of activated T cells to a very similar degree and respond to pro-inflammatory stimulation by enhancing their anti-inflammatory activity. These results suggest that testing MSC transplantation in naturally occurring immune-mediated diseases in dogs may have high translational value for human clinical trials.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of neurological disability, and current treatments have limited effectiveness. Recent studies have emphasized the potential of exosomes derived from umbilical cord mesenchymal stem cells (UC-MSCs-Exo) in TBI treatment, but the molecular mechanisms underlying their therapeutic effects are not fully understood.
RESULTS: In this study, UC-MSCs-Exo was isolated using ultracentrifugation and intraventricularly injected to TBI rat model. The neurofunctional motor function of the rats was evaluated using the modified neurological severity score (mNSS), and the activation of microglia was assessed through immunofluorescence detection of IBA1 expression levels. Additionally, we established an in vitro neuroinflammatory model using BV2 microglia to investigate the effects of UC-MSCs-Exo and miRNA-21. Our findings indicate that UC-MSCs-Exo promote neurological recovery in TBI rats and inhibit excessive microglia activation. Furthermore, UC-MSCs-Exo highly expresses miRNA-21 and inhibited the proliferation, migration, and release of inflammatory mediators of BV2 microglia by transporting miRNA-21.
CONCLUSIONS: The present study suggests that the promotion of neurological recovery in TBI rats by UC-MSCs-Exo may be attributed to the inhibition of excessive microglia activation through miRNA-21.