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Synergistic Improvement in Children with Cerebral Palsy Who Underwent Double-Course Human Wharton's Jelly Stem Cell Transplantation.

ABSTRACT: Background:Our previous studies confirmed that human Wharton's Jelly stem cell (hWJSC) transplantation improved motor function in children with spastic cerebral palsy (CP). This study investigated the dose-effect relationship between the transplanted cell dosage and efficacy in CP children. Methods:CP children who received one- or two-course (four or eight times lumbar puncture, 4 or 8 × 107?hWJSCs) cell therapy were recruited into this study. Assessments of motor function were performed according to scales for gross motor function measurement (GMFM) and fine motor function measurement (FMFM). The measurement data obtained in the two different groups were analyzed by t-test. Univariate repeated measures analysis of variance was used to compare the data obtained at baseline and 6 or 12 months posttransplantation and met the conditions for Mauchly's sphericity test. Results:The results for fifty-seven pediatric CP patients (including 35 male and 22 female patients) who completed follow-up showed that gross and fine motor functions improved after cell therapy. Interestingly, the GMFM and FMFM scores in patients who received one course of transplantation were significantly increased at 6 months after treatment. Moreover, another course of transplantation further improved gross and fine motor function in children. The scores for GMFM and FMFM were significantly higher at 6 months posttransplantation than at baseline and showed a linear upward trend. There was no gender difference in GMFM. Interestingly, there was a significant difference between male and female patients in the B and C dimensions of FMFM. These results reveal a gender-related susceptibility to stem cell therapy, especially for movement capability of the upper extremity joint and grasping ability. Similarly, in the group aged ?3 years old, the improvement observed in dimension A (lying and rolling) of GMFM was nearly exponential and showed a quadratic trend. The results for FMFM were similar to those for GMFM. Moreover, the improvement in motor function was not age dependent. Conclusions:In this study, our data collectively reveal that CP children display sex- or age-dependent responses to hWJSC therapy; these results shed light on the clinical utility of this approach in specific populations.

SUBMITTER: Fu X

PROVIDER: S-EPMC6766101 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Synergistic Improvement in Children with Cerebral Palsy Who Underwent Double-Course Human Wharton's Jelly Stem Cell Transplantation.

Fu Xiaojun X Hua Rongrong R Wang Xiaodong X Wang Peishen P Yi Long L Yu Aixue A Yang Jing J Li Yan Y An Yihua Y

Stem cells international 20190917

<h4>Background</h4>Our previous studies confirmed that human Wharton's Jelly stem cell (hWJSC) transplantation improved motor function in children with spastic cerebral palsy (CP). This study investigated the dose-effect relationship between the transplanted cell dosage and efficacy in CP children.<h4>Methods</h4>CP children who received one- or two-course (four or eight times lumbar puncture, 4 or 8 × 10<sup>7</sup> hWJSCs) cell therapy were recruited into this study. Assessments of motor funct ...[more]

PMID: 31636676

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Project description:IntroductionCell-based therapy was a promising treatment method for disc degenerative diseases. Wharton's jelly cell (WJC) has been explored to cure various human diseases, while it still remains unknown about this MSC for disc repair. In our prior work, WJCs could differentiate into nucleus pulposus (NP)-like cells by co-culturing with NP cells in vitro. Thence, the aim of this study was further to investigate the survival and function of WJCs in vivo after transplantation into degenerated canine discs.MethodWJCs were isolated from human umbilical cords and labeled with EGFP. The degeneration of L4-5, L5-6, and L6-7 discs of beagles was induced by aspirating the NP tissues. Four weeks after the operation, the injured discs were left to be no treatment at L4-5 (DS group), injected with 0.9 % saline at L5-6 (FS group), and transplanted with EGFP-labeled WJCs at L6-7 (TS group). In all animals, the intact disc L3-4 served as a control (CS group). The animals were followed up for 24 weeks after initial operation. Spine imaging was evaluated at 4, 8, 12, and 24 weeks, respectively. Histologic, biomechanics and gene expression analyses were performed at 24 weeks. Immunohistochemistry for aggrecan, types II collagen, SOX-9 was employed to investigate the matrix formation in the NP.ResultsThe TS group showed a significantly smaller reduction in the disc height and T2-weighted signal intensity, and a better spinal segmental stability than DS and FS groups. Histologic assay demonstrated that WJCs were specifically detected in TS group at 24 weeks and the discs of TS group maintained a relatively well preserved structure as compared to the discs of DS and FS groups. Furthermore, real-time PCR and immunohistochemistry demonstrated that expressions of disc matrix genes, aggrecan, type II collagen, and SOX-9, were up-regulated in TS group compared to DS and FS groups.ConclusionWJCs could not only survive in the degenerate IVDs, but also promote the disc matrix formation of aggrecan and type II collagen in the degenerate IVDs. It may have value in cell-based therapy for degenerative disc disease.

Project description:The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI).In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively.During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group [6.9 ± 0.6 % (95 %CI, 5.7 to 8.2)] and [7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group [3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001] and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002] at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0.001]. Concomitantly, the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group (P = 0.0004, P = 0.004, respectively).Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy.Clinical Trials NCT01291329 (02/05/2011).

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Synergistic Improvement in Children with Cerebral Palsy Who Underwent Double-Course Human Wharton's Jelly Stem Cell Transplantation.

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Synergistic Improvement in Children with Cerebral Palsy Who Underwent Double-Course Human Wharton's Jelly Stem Cell Transplantation.

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