Umbilical Cord Blood-derived Mesenchymal Stem Research Articles

Effect of preoperative medial meniscus status on the outcomes of high tibial osteotomy with human umbilical cord-derived mesenchymal stem cells cartilage regeneration.

The effect of medial meniscus (MM) status on outcomes following high tibial osteotomy (HTO) combined with cartilage regeneration using human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) remains unclear. This study aimed to evaluate the effect of preoperative MM status on the outcomes of HTO combined with cartilage regeneration using hUCB-MSCs. Specifically, clinical and radiological outcomes were compared between two groups of patients, which were divided according to their preoperative MM status. We hypothesized that patients with preserved meniscal integrity or those who underwent meniscal root repair would show better clinical and radiological outcomes compared to those with significant meniscal loss or untreated root tears. A retrospective analysis was performed on 47 patients who underwent HTO with hUCB-MSC implantation. Patients were divided into group P (preserved MM integrity or medial meniscal root repair) and group L (loss of MM integrity, defined as a peripheral rim width <3 mm, unable to maintain hoop function). Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores after a minimum follow-up of 2 years. Cartilage regeneration was evaluated with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score and International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) score from second-look arthroscopy. Correlation analyses were conducted to examine the relationship between preoperative MM extrusion and cartilage repair. Both groups demonstrated significant improvements in IKDC and WOMAC scores (p < 0.01). No significant differences were observed between groups in IKDC and WOMAC scores at final follow-up (p = 0.21, p = 0.42, respectively). MOCART 2.0 and ICRS CRA scores showed no significant differences between groups (p = 0.35, p = 0.08, respectively). Group P showed higher proportions of favorable outcomes compared to group L, including no major subchondral changes or only minor marrow edema (56% vs. 31.8%) and ICRS CRA grades I or II (84% vs. 72.7%). While these findings suggest potential differences in outcomes, neither comparison reached statistical significance (p = 0.09 and p = 0.48, respectively). Preoperative MM extrusion negatively correlated with MOCART 2.0 and subchondral bone changes (r = -0.24, p = 0.03; r = -0.285, p = 0.02, respectively). HTO with hUCB-MSC implantation provided significant clinical improvements and effective cartilage regeneration regardless of preoperative MM status. However, preoperative MM extrusion may influence subchondral bone changes, emphasizing the need to consider MM status for long-term outcomes. III; retrospective comparative study.

Protective effects and possible mechanisms of mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles against kidney fibrosis in animal models: a systematic review and meta-analysis.

The risk of kidney fibrosis is significantly elevated in individuals with diabetes, chronic nephritis, trauma, and other underlying conditions. Concurrently, human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and their extracellular vesicles (MSC-Exos) have gained prominence in regenerative medicine. In light of these observations, we are undertaking a meta-analysis to elucidate the influence of hUCB-MSCs and MSC-Exos on kidney fibrosis. To identify eligible trials, we conducted a comprehensive search of the CNKI, PubMed, Web of Science and Wanfang databases from inception to 24 October 2022. Furthermore, the methodological quality of the included studies was evaluated using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool. Besides, the weighted standard mean difference (SMD) with a 95% confidence interval (CI) was calculated using the Review Manager 5.4 software. The Stata (12.0) software was employed to assess the impact of factors on outcome heterogeneity and publication bias in the study. A total of 645 related research studies were retrieved, of which 14 that involved 219 experimental animals were included in the study. In comparison to the control treatment, treatment with Human UCB MSC and MSC-Exos was observed to significantly enhance renal function in animal models of kidney fibrosis. This was evidenced by a reduction in serum creatinine (Scr) levels (p < 0.00001) and blood urea nitrogen (BUN) levels (p < 0.00001), as well as reduction of CD68+ macrophages (p < 0.00001), TdT-mediated dUTP Nick-End labeling (TUNEL)+ tubular cells(p < 0.00001), α-SMA levels (p = 0.0009) and TGF-β1 (p < 0.00001). P < 0.05 is deemed to indicate a statistically significant difference. Alpha-smooth muscle actin (α-SMA) is a specific protein that is normally expressed in myofibroblasts. The term "CD68+ macrophages" refers to macrophages that express the CD68 protein on their cell surface. Both macrophages and myofibroblasts have been linked to the development of kidney fibrosis. In this study, the quantity of CD68+ macrophages and α-SMA was employed as a means of gauging the extent of renal fibrosis. Additionally, transforming growth factor beta 1 (TGF-β1) is a significant cytokine implicated in the pathogenesis of kidney fibrosis. TUNEL-positive tubular cells represent tubular cells undergoing apoptosis. It is hypothesized that this may result in a reduction of tubular apoptosis and a delay in kidney fibrosis, due to the inhibition of the transformation of macrophages into myofibroblasts (MMT) and the disruption of the kidney fibrogenic niche. The principal findings of this preclinical systematic review indicate that hUCB MSC and MSC-Exos have a substantial protective impact against kidney fibrosis. Kidney transfer remains the final option for traditional renal fibrosis treatment. The lack of donors and high cost make it challenging for many patients to access appropriate treatment. Although this study still suffers from three shortcomings: sample size, methodological consistency and translational challenges, the hUCB MSC and MSC-Exos have been demonstrated to reduce tubular apoptosis and inhibit fibrotic progression. The hUCB MSC and MSC-Exos offer a promising alternative due to their lower price and accessibility. Nevertheless, further high-quality studies are required in the future to address the methodological limitations identified in this review. Identifier INPLASY2022100104.

Chondrogenic commitment of human umbilical cord blood and umbilical cord-derived mesenchymal stem cells induced by the supernatant of chondrocytes: A comparison study.

Native cartilage has low capacity for regeneration because it has very few progenitor cells. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and human umbilical cord-derived MSCs (hUC-MSCs) have been employed as promising sources of stem cells for cartilage injury repair. Reproduction of hyaline cartilage from MSCs remains a challenging endeavor. The paracrine factors secreted by chondrocytes possess the capability to induce chondrogenesis from MSCs. The conditioned medium derived from chondrocytes was utilized to induce chondrogenic differentiation of hUCB-MSCs and hUC-MSCs. The expression levels of collagen type I alpha 1 chain (Col1a1), collagen type II alpha 1 chain (Col2a1), and SRY-box transcription factor 9 (SOX9) were assessed through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunofluorescence (IF) assays. To elucidate the mechanism of differentiation, the concentration of transforming growth factor-β1 (TGF-β1) in the conditioned medium of chondrocytes was quantified using enzyme-linked immunosorbent assay (ELISA). Meanwhile, the viability of cells was assessed using Cell Counting Kit-8 (CCK-8) assays. The expression levels of Col2a1 and SOX9 were found to be higher in induced hUC-MSCs compared to those in induced hUCB-MSCs. The conditioned medium of chondrocytes contained TGF-β1. The CCK-8 assays revealed that the proliferation rate of hUC-MSCs was significantly higher compared to that of hUCB-MSCs. The chondrogenic potential and proliferation capacity of hUC-MSCs surpass those of hUCB-MSCs, thereby establishing hUC-MSCs as a superior source of seed cells for cartilage tissue engineering.

Machine Learning and Metabolomics Predict Mesenchymal Stem Cell Osteogenic Differentiation in 2D and 3D Cultures.

Stem cells have been widely used to produce artificial bone grafts. Nonetheless, the variability in the degree of stem cell differentiation is an inherent drawback of artificial graft development and requires robust evaluation tools that can certify the quality of stem cell-based products and avoid source-tissue-related and patient-specific variability in outcomes. Omics analyses have been utilised for the evaluation of stem cell attributes in all stages of stem cell biomanufacturing. Herein, metabolomics in combination with machine learning was utilised for the benchmarking of osteogenic differentiation quality in 2D and 3D cultures. Metabolomics analysis was performed with the use of gas chromatography-mass spectrometry (GC-MS). A set of 11 metabolites was used to train an XGboost model which achieved excellent performance in distinguishing between differentiated and undifferentiated umbilical cord blood mesenchymal stem cells (UCB MSCs). The model was benchmarked against samples not present in the training set, being able to efficiently capture osteogenesis in 3D UCB MSC cultures with an area under the curve (AUC) of 82.6%. On the contrary, the model did not capture any differentiation in Wharton's Jelly MSC samples, which are well-known underperformers in osteogenic differentiation (AUC of 56.2%). Mineralisation was significantly correlated with the levels of fumarate, glycerol, and myo-inositol, the four metabolites found most important for model performance (R2 = 0.89, R2 = 0.94, and R2 = 0.96, and p = 0.016, p = 0.0059, and p = 0.0022, respectively). In conclusion, our results indicate that metabolomics in combination with machine learning can be used for the development of reliable potency assays for the evaluation of Advanced Therapy Medicinal Products.

Anterior to Central Cartilage Defects of Arthritic Knee Showed Better Cartilage Regeneration Than Posterior Cartilage Defects using Mesenchymal Stem Cell Implantation

PurposeTo analyze cartilage regeneration and clinical outcomes after human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) implantation based on the distribution and location of medial femoral condyle (MFC) cartilage defects. MethodsPatients who underwent hUCB-MSC implantation for MFC cartilage defects involved in isolated medial compartment osteoarthritis were included. The patients were divided into two groups: those with MFC defects located within the anterior-central portion (Group A) and those with MFC defects extending to the posterior portion (Group P). Cartilage regeneration was assessed using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 scores. MFC cartilage defects were subdivided into anterior, central, and posterior regions. The total, regional MOCART scores, and patient-reported outcomes (PROs) were evaluated. ResultsOverall, 43 patients were included in this study (Group A: 31 patients, Group P: 12 patients), with 30/43 undergoing combined high tibial osteotomy. Cartilage defect size was significantly larger in Group P than in Group A (7.8±1.9 cm2 vs. 5.7±2.4 cm2, P=0.009). Group A demonstrated a significantly higher total MOCART score compared to Group P (55.0±12.3 vs. 40.4±9.2, P=0.001). PROs at final follow-up showed significant improvement compared to preoperative values in both groups (all P<0.001), with no significant differences in PROs between groups. The mean follow-ups for each group were 29.7 and 32.5 months, respectively. Defect size were significantly associated with the total MOCART score (P=0.026) and unsatisfactory outcome (MOCART < 60) (P=0.012, odds ratio 2.674). The cut-off value for defect size was 6.3 cm2 (area under the curve, 0.905; P<0.001). In the comparison of regional MOCART scores within each patient, the anterior MOCART score was significantly higher than the central and posterior MOCART scores (P<0.001 and P=0.004, respectively). ConclusionCartilage defects with osteoarthritis, which is smaller and primarily limited to the anterior-to-central portion showed better MOCART scores after hUCB-MSC implantation.

Exploring Mesenchymal Stem Cells versus Minoxidil for Androgenic Alopecia Treatment: A Detailed Animal-Based Histological and Morphometric Study

Introduction: Androgenic alopecia (AGA), a hair loss condition caused by dihydrotestosterone binding to hair follicle receptors, negatively impacts quality of life for both men and women. Current treatments like minoxidil and finasteride have limitations, highlighting the need for alternative therapies, such as human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs). Methods: In this study, forty-eight adult male Wistar albino rats (3 months old) were used. The control group (Group I) received no treatment, while the other rats underwent AGA induction via daily subcutaneous testosterone injections (100 mg/kg). These rats developed alopecia and were divided into three groups: AGA (Group II), AGA plus daily minoxidil spray (Group III), and AGA plus a single intradermal injection of HUCB-MSCs (1 mL containing 1 × 105 cells, Group IV). After 4 weeks, the rats were sacrificed, and skin specimens were prepared for histological analysis using H&E, Masson’s trichrome, and immunohistochemical staining for CK 19, vascular endothelial growth factor (VEGF), and TUNEL antibodies. Results: It was shown that HUCB-MSC treatment reversed structural damage to hair and follicles, normalizing conditions within 1-week post-injection. The treatment enhanced the anagen phase, suppressed telogen and catagen phases, reduced apoptosis, and increased VEGF and CK 19 immune reactions. Observational follow-up for Groups III and IV revealed that while the minoxidil group experienced significant hair loss after 37 days, the stem cell group exhibited dense and long hair covering the treated area. Conclusion: HUCB-MSC therapy demonstrated superior efficacy over minoxidil with no observed side effects, indicating its potential as a promising alternative for AGA treatment.

Effect of mesenchymal stem cell derived from umbilical cord blood on rabbit intrauterine adhesion model

Objective: To investigate the repair effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSC) on endometrium of intrauterine adhesion (IUA) by establishing animal model. Methods: Eighteen healthy female New Zealand white rabbits were divided into a control group, an IUA group and an hUCB-MSC transplantation group according to random number table method. The control group underwent laparotomy only. The IUA group underwent IUA modeling surgery using curettage and lipopolysaccharide (LPS) cotton placed in uterine cavity for double injury. The hUCB-MSC transplantation group received the same IUA modeling surgery followed by multipoint injection of hUCB-MSC suspension (2×106 cells/ml, 500 μl) into the bilateral uterine myometrium one week after surgery. Four weeks after the IUA modeling surgery, the rabbits were euthanized and samples were collected. Hematoxylin and eosin (HE) staining and Masson staining were used to assess the number of endometrial glands and the fibrosis rate. RNA sequencing was performed on the endometrium of the IUA group and hUCB-MSC transplantation group.The mRNA and protein expression of the fibrosis markers [transforming growth factor β1 (TGF-β1) and tissue inhibitors of metalloproteinase 1 (TIMP1)] and RNA sequencing-related parameters were detected by quantitative real-time PCR (qRT-PCR) and Western blot. Results: Compared with the control group, the number of glands in IUA group decreased (26.33±1.53 vs 4.33±1.53, P<0.001), and the fibrosis rate increased (18.01%±2.21% vs 69.55%±2.42%, P<0.001), indicating successful modeling. HE and Masson staining revealed that the number of glands in the hUCB-MSC transplantation group was increased compared with that in IUA group (17.33±2.52 vs 4.33±1.53, P<0.001), and the fibrosis rate decreased (69.55%±2.42% vs 41.55%±1.99%,P=0.001). Western blot analyses of fibrosis-related proteins (TGF-β1 and TIMP1) showed elevated levels of TGF-β1 (0.91±0.05) and TIMP1 (0.99±0.01) proteins in the IUA group compared to control group (0.61±0.04, 0.68±0.07) (P=0.001, 0.015). The hUCB-MSC transplantation group exhibited reduced expression of TGF-β1 (0.69±0.04) and TIMP1 (0.62±0.08) proteins compared to the IUA group (P=0.005, 0.014). Western Blot results related to the PI3K/AKT signaling pathway [phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT)] showed that the expression of p-PI3K(1.05±0.05) and p-AKT(1.17±0.06) in the IUA group increased compared to the control group (0.78±0.03, 0.85±0.05) (P=0.002, 0.002). The expression of p-PI3K (0.74±0.02) and p-AKT (0.93±0.04) proteins in the hUCB-MSC transplantation group decreased compared to the IUA group (P=0.003, 0.005). Conclusion: hUCB-MSC can repair the damaged endometrium in rabbit intrauterine adhesion model by increasing the number of endometrial glands and improving its level of fibrosis.

Effect of Mesenchymal Stem Cells in Androgenic Induced Alopecia in Adult Male Albino Rats versus Conventional Minoxidil Treatment

Abstract Background Androgenic alopecia (AGA) could be the most common form of hair loss in man. AGA could be associated with reduced quality of life. Might cause several psychological comorbidities such as depression, anxiety. There are two FDA approved medications for treatment of hair loss; minoxidil (antihypertensive &amp; vasodilator) in addition to finasteride (a selective inhibitor of type II &amp; III isoforms of 5α-reductase enzyme). Aim of Work The current study was performed to investigate the potential role of human umbilical cord blood-derived mesenchymal stem cells (hUCB)-MSCs in aiding hair growth in AGA compared to conventional minoxidil treatment in adult male albino rats. Material and Methods Forty-eight adult male albino rats were used in the study. Rats were assigned into the following groups; control group that either received no treatment or daily subcutaneous injection of sesame oil (0.1 ml), AGA group in which rats received daily subcutaneous injection of testosterone in a dose of 2 mg/rat /day, AGA plus Minoxidil treatment group in which rats received testosterone injection as in group II in addition to 2% Minoxidil spray treatment, AGA plus hUCB-MSCs treatment group in which rats received testosterone injection in addition to dermal injection of 1 x105 cells /cm2 of stem cells. At the end of the experiment after 2 weeks, rats were sacrificed for paraffin blocks and stained with H &amp; E and Masson’s Trichrome. Results Decrease in both total number of hair follicles and number of anagen hair follicles was noticed. There was an increase in mean number of the telogen hair follicles. There were increase in the catagen hair follicles with numerous fibrous streamers observed, with increased vellus hair number. Meanwhile, terminal hair number had been decreased in comparison to control group. There were cavitations in hairs and their sheaths, inter follicular cavitation, wavey collagen fiber deposition, perifollicular mononuclear cell infiltrate, and thinning of arrector pili muscle. Conclusion Stem cell therapy had superior efficacy over minoxidil in the treatment of AGA.

Umbilical Cord Blood Mesenchymal Stem Cells Mitigated Diabetic Hepato-Renal Insufficiency in Alloxan-Induced Type 1 Diabetes in Dogs: Biochemical and Histopathological Approach

Umbilical Cord Blood Mesenchymal Stem Cells Mitigated Diabetic Hepato-Renal Insufficiency in Alloxan-Induced Type 1 Diabetes in Dogs: Biochemical and Histopathological Approach

Novel Treatment Options for Knee Cartilage Defects in 2023.

Articular cartilage lesions are a common injury that have become increasingly treatable with joint preservation procedures. Well-documented allograft and cellular treatments for these lesions are detailed elsewhere in this volume. This article discusses three new unique options for addressing these defects taking three different paths to address these complex injuries. Agili-C is an existing FDA- and EMEA-approved option using an acellular aragonite-based scaffold to treat both chondral and osteochondral lesions, with or without concurrent arthritis. Cartistem is a stem-cell-based product composed of culture-expanded allogeneic human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel, which is in its final clinical trial stages in the United States, but already has regulatory approval in Korea. IMPACT and RECLAIM studies have shown the safety and efficacy of a new one-stage procedure utilizing autologous chondrons combined with allogeneic mesenchymal stem cells (MSCs) that can provide another effective single-stage treatment option.

Human umbilical cord blood mesenchymal stem cells mediate microglia activation and improve anxiety-like behavior in MIA-induced offspring of schizophrenic rats

Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model. Open field, PPI, Western blotting, Q-PCR, and immunofluorescence were used to assess the biological effects of repeated tail vein injections of hUC-MSC in offspring rats following the MIA model of SCZ. The results indicated that offspring of MIA rats exhibited schizophrenia-like (SCZ-like) anxiety behavior, with observed microglial activation triggering neuroinflammation. Furthermore, levels of IBA1, HMGB1, and PSD95 were significantly up-regulated, while SYP was significantly down-regulated. It is suggested that hUCB-MSCs may act through HMGB1, Iba1, PSD95, and related pathway molecules to alleviate neuroinflammation and repair synaptic damage by regulating the activity state of microglia. Consequently, this could improve the abnormal behavior observed in MIA offspring rats.

NUFIP1-engineered exosomes derived from hUMSCs regulate apoptosis and neurological injury induced by propofol in newborn rats

BackgroundPropofol can increase neurotoxicity in infants but the precise mechanism is still unknown. Our previous study revealed that nuclear FMR1 interacting protein 1 (NUFIP1), a specific ribophagy receptor, can alleviate T cell apoptosis in sepsis. Yet, the effect of NUFIP1-engineered exosomes elicited from human umbilical cord blood mesenchymal stem cells (hUMSCs) on nerve injury induced by propofol remains unclear. This study intended to investigate the effect of NUFIP1-engineered exosomes on propofol-induced nerve damage in neonatal rats. MethodsFirstly, NUFIP1-engineered exosomes were extracted from hUMSCs serum and their identification was conducted using transmission electron microscopy (TEM), Flow NanoAnalyzer, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB). Subsequently, the optimal exposure duration and concentration of propofol induced apoptosis were determined in SH-SY5Y cell line using WB. Following this, we co-cultured the NUFIP1-engineered exosomes in the knockdown group (NUFIP1-KD) and overexpression group (NUFIP1-OE) with SH-SY5Y cells and assessed their effects on the apoptosis of SH-SY5Y cells using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay, Hoechst 33258 staining, WB, and flow cytometry, respectively. Finally, NUFIP1-engineered exosomes were intraperitoneally injected into neonatal rats, and their effects on the learning and memory ability of neonatal rats were observed through the righting reflex and Morris water maze (MWM) test. Hippocampi were extracted from different groups for hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence, and WB to observe their effects on apoptosis in neonatal rats. ResultsTEM, Flow NanoAnalyzer, qRT-PCR, and WB analyses confirmed that the exosomes extracted from hUMSCs serum exhibited the expected morphology, diameter, surface markers, and expression of target genes. This confirmed the successful construction of NUFIP1-KD and NUFIP1-OE-engineered exosomes. Optimal exposure duration and concentration of propofol were determined to be 24 hours and 100 µg/ml, respectively. Co-culture of NUFIP1 engineered exosomes and SH-SY5Y cells resulted in significant up-regulation of pro-apoptotic proteins Bax and c-Caspase-3 in the KD group, while anti-apoptotic protein Bcl-2 was significantly decreased. The OE group showed the opposite trend. TUNEL apoptosis assay, Hoechst 33258 staining, and flow cytometry yielded consistent results. Animal experiments demonstrated that intraperitoneal injection of NUFIP1-KD engineered exosomes prolonged the righting reflex recovery time of newborn rats, and MWM tests revealed a significant diminution in the time and number of newborn rats entering the platform. HE staining, immunohistochemistry, immunofluorescence, and WB results also indicated a significant enhancement in apoptosis in this group. Conversely, the experimental results of neonatal rats in the OE group revealed a certain degree of anti-apoptotic effect. ConclusionsNUFIP1-engineered exosomes from hUMSCs have the potential to regulate nerve cell apoptosis and mitigate neurological injury induced by propofol in neonatal rats. Targeting NUFIP1 may hold great significance in ameliorating propofol-induced nerve injury.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24and 48 weeks. Secondary outcomes included arthroscopic, histologicaland magnetic resonance imaging assessments at 1 year. Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignmentand clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. Level II, Prospective Comparative Cohort Study.

Prognostic Factors for Clinical Outcome and Cartilage Regeneration after Implantation of Allogeneic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Large-Sized Cartilage Defects with Osteoarthritis.

To analyze the prognostic factors for clinical outcomes and cartilage regeneration after the implantation of allogeneic human umbilical cord blood mesenchymal stem cell (hUCB-MSC) for treating large-sized cartilage defects with osteoarthritis. This study is a case-series with multiple subgroup analyses that divides the included patients into multiple subgroups based on various factors. Overall, 47 patients who underwent hUCB-MSC implantation were included. The patient-reported outcomes, magnetic resonance imaging (MRI), and second-look arthroscopy were used to assess the outcomes. Combined realignment surgery significantly correlated with clinical outcomes, particularly pain. No other factors significantly influenced the clinical outcomes in short-term period. Subgroups with large defect sizes or meniscal insufficiency showed significantly poor MRI and arthroscopy outcomes (MRI, P = 0.001, P = 0.001; arthroscopy, P = 0.032, P = 0.042). The logistic regression showed that patients with a 1 cm2 larger defect size were 1.91 times less likely to achieve favorable MRI outcomes (P = 0.017; odds ratio [OR], 1.91). Cut-off value to predict the poor outcome was >5.7 cm2 (area under the curve, 0.756). A cartilage defect size >5.7 cm2 was the major poor prognostic factor for cartilage regeneration on MRI (P = 0.010; OR, 17.46). If the postoperative alignment shifted by 1° opposite to the cartilage defect, it was 1.4 times more likely to achieve favorable MRI outcomes (P = 0.028; OR, 1.4). Combining realignment surgery showed a better prognosis for pain improvement. Cartilage defect size, meniscal function, and postoperative alignment are significant prognostic factors for cartilage regeneration. A cartilage defect size >5.7 cm2 was significantly related to poor cartilage regeneration.

Allogeneic umbilical cord blood-derived mesenchymal stem cell implantation versus microdrilling combined with high tibial osteotomy for cartilage regeneration

This study compared cartilage regeneration outcomes in knee osteoarthritis (OA) using allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation and microdrilling with high tibial osteotomy (HTO). Fifty-four patients (60 knees) were included: 24 (27 knees) in the hUCB-MSC group and 30 (33 knees) in the microdrilling group. Both groups showed significant improvements in pain and functional scores at 6, 12, and 24 months compared to baseline. At 24 months, the hUCB-MSC group had significantly improved scores. Arthroscopic assessment at 12 months revealed better cartilage healing in the hUCB-MSC group. In subgroup analysis according to the defect site, hUCB-MSC implantation showed superior cartilage healing for anterior lesions. In conclusion, both treatments demonstrated effectiveness for medial OA. However, hUCB-MSC implantation had better patient-reported outcomes and cartilage regeneration than microdrilling. The study suggests promising approaches for cartilage restoration in large knee defects due to OA.

Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats.

Cisplatin-containing regimen is an effective treatment for several malignancies. However, cisplatin is an important cause of nephrotoxicity. So, many trials were performed to transplant stem cells systemically or locally to control cisplatin-induced nephrotoxicity. Stem cell therapeutic effect may be dependent on the regulation of inflammation and oxidant stress. To investigate the effect of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) on the histological structure, the oxidant stress, and the inflammatory gene expression in an experimental model of cisplatin-induced nephrotoxicity in rats. The rats were divided into 6 equal groups (each of 10 rats): Group I included normal rats that received no treatment. Group II included healthy rats that received IV hUCB-MSCs. Group III included untreated cisplatin-induced nephrotoxic rats. Group IV included cisplatin-induced nephrotoxic rats that received magnesium (Mg) injections after injury. Group V was injected with hUCB-MSCs after injury. Group VI received both Mg and hUCB-MSCs after injury. In tissue homogenates, reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) activities were measured. Quantitative real-time-polymerase chain reaction (qRT-PCR) was performed to assess iNOS, TLR4, and NF-kB gene expression. Hematoxylin and eosin (H&E) staining was performed to study the histological structure of the kidney. Immunohistochemical staining of iNOS and NF-κB was performed, as well. Disturbed kidney functions, oxidative status, and histological structure were seen in the rats that received cisplatin. Treated groups showed improvements in kidney functions, oxidative status, and histological structure, particularly in the combined treatment group. In the cisplatin-induced nephrotoxicity model, hUCB-MSCs could improve the functional and morphological kidney structure by modulation of oxidative and inflammatory status.

Exosomes derived from miR-133a-3p engineered mesenchymal stem cells promote myocardial repair in rats after acute myocardial infarction

Objective: To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats. Methods: UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results: Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion: Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

Effects of Extracellular Vesicles Derived from Human Umbilical Cord Blood Mesenchymal Stem Cells on Cell Immunity in Nonobese Mice.

Autoimmune responses are the most important pathogenic mechanisms underlying type 1 diabetes (T1D). Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have immunomodulatory effects. In this study, we investigated whether EVs derived from human umbilical cord MSCs (HucMSC-EVs) have treatment effects on nonobese diabetic (NOD) mice as model of T1D. HucMSC-EVs were isolated from human umbilical cord MSCs and characterized. NOD mice (aged 4 weeks) were administered with HucMSC-EVs or the same volume of phosphate-buffered saline (PBS) via caudal vein injection twice per week. After 8 weeks of treatment, blood, spleen, and pancreatic samples were collected. Mouse blood glucose levels and body weights were measured during treatment, and insulin concentration and inflammatory cytokine levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) staining were used to evaluate pathological changes in mouse islets. T lymphocyte subsets were evaluated by flow cytometry, while quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analyses were used to detect the expression of transcription factor and inflammatory cytokines. Our data indicated that HucMSC-EVs treatment reduced blood glucose levels and increased insulin concentration in NOD mice. Levels of interleukin-2 (IL-2), IL-4, and IL-10 were significantly increased and those of IL-1β and interferon-γ (IFN-γ) significantly decreased in the HucMSC-EVs group. The positive ratio of CD4+ T lymphocyte subsets decreased after intravenous injection of HucMSC-EVs, in which the proportion of Th2 cells increased and that of Th1 decreased. GATA-3 and IL-2, IL-4 and IL-10 expression levels were upregulated in spleen on treatment with HucMSC-EVs, whereas those of T-bet and IFN-γ were downregulated. In addition, more inflammatory cell infiltration was detected in the pancreas of control group mice than those treated with HucMSC-EVs. IHC staining showed that Fas/FasL expression and distribution in control group pancreas were higher than those in the HucMSC-EVs group. Together, our findings indicate that HucMSC-EVs have potential to prevent islet injury via T cell immune responses by adjusting the Th1/Th2 ratio to regulate secretion of inflammatory factors.

Human umbilical cord blood-derived mesenchymal stem cells therapy for cerebral infarction in animal model: A meta-analysis

Aim: Cerebral infarction (CI) is a serious cerebrovascular infarction disease. In recent years, the use of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) has received attention as a new alternative for treating CI in animal model. This systematic review evaluated the efficacy and safety of hUCB-MSCs, using as a treatment in improving functional recovery of CI in animal model. Methods: Electronic databases through July 5, 2023 were searched to identify relevant studies that controlled hUCB-MSCs treatment studies focusing on CI in animal model. We independently selected and assessed the relevant studies. Results: 27 studies that fulfilled the inclusion criteria were included. Compared with control group, significant beneficial effects were observed in hUCB-MSCs group regarding the neurological deficit scores (mean difference [MD]: −1.57, 95% confidential interval [CI]: −2.06, −1.08, P&lt;0.00001), infarct size (MD: −2.82, 95% CI: −4.14, −1.49, P&lt;0.0001).