scholarly journals Regeneration of a Full-Thickness Defect of Rotator Cuff Tendon with Freshly Thawed Umbilical Cord-Derived Mesenchymal Stem Cells in a Rat Model

2020 ◽  
Author(s):  
Ji-Hye Yea ◽  
Jin-Kyung Park ◽  
InJa Kim ◽  
Gayoung Sym ◽  
Tae Soo Bae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Umbilical Cord ◽  
Rat Model ◽  
Animal Experiments ◽  
Surrounding Tissue ◽  
Control Group ◽  
Full Thickness ◽  
Rotator Cuff Tendon

Abstract Background: It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. Methods: We evaluated morphology, viability and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus tendon of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs respectively. Two to four weeks later, macroscopic, histological and biomechanical changes were evaluated. T-test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant.Results: T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was further recovered at two and four weeks such as inflammation, defect size, neighboring tendon, swelling/redness and the connecting surrounding tissue and slidability. Histologically, compared to the control group the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization and fiber coherence were improved by 33.33%, 42.75%, 1.86- and 1.99-fold and GAG-rich area was suppressed by 81.05% at four weeks. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both two and four weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Conclusions: The morphology, viability and proliferation of T-UC MSCs are comparable to those of C-UC MSCs. Treatment with T-UC MSCs induces tendon regeneration of FTD at the macroscopic, histological and biomechanical levels comparable to treatment with C-UC MSCs.

scholarly journals Regeneration of a full-thickness defect of rotator cuff tendon with freshly thawed umbilical cord-derived mesenchymal stem cells in a rat model

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-Hye Yea ◽  
Jin-Kyung Park ◽  
In Ja Kim ◽  
Gayoung Sym ◽  
Tae-Soo Bae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Umbilical Cord ◽  
Rat Model ◽  
Animal Experiments ◽  
Surrounding Tissue ◽  
Control Group ◽  
Full Thickness ◽  
Rotator Cuff Tendon

Abstract Background It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. Methods We evaluated morphology, viability, and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs, respectively. Two and 4 weeks later, macroscopic, histological, biomechanical, and cell trafficking were evaluated. T test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant. Results T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was more recovered at 2 and 4 weeks such as inflammation, defect size, neighboring tendon, swelling/redness, the connecting surrounding tissue and slidability. Histologically, the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization, and fiber coherence were improved by 33.33%, 42.75%, 1.86-fold, and 1.99-fold at 4 weeks, and GAG-rich area decreased by 88.13% and 94.70% at 2 and 4 weeks respectively. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both 2 and 4 weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Moreover, T-UC MSCs remained 8.77% at 4 weeks after injury, and there was no significant difference between C-UC MSCs and T-UC MSCs. Conclusions The morphology, viability, and proliferation of T-UC MSCs were comparable to those of C-UC MSCs. Treatment with T-UC MSCs could induce tendon regeneration of FTD at the macroscopic, histological, and biomechanical levels comparable to treatment with C-UC MSCs.

scholarly journals Regeneration of a Full-thickness Defect of Rotator Cuff Tendon with Freshly Thawed Umbilical Cord-Derived Mesenchymal Stem Cells in a Rat Model

2020 ◽  
Author(s):  
Ji-Hye Yea ◽  
Jin-Kyung Park ◽  
InJa Kim ◽  
Gayoung Sym ◽  
Tae Soo Bae ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Umbilical Cord ◽  
Rat Model ◽  
Full Thickness ◽  
Rotator Cuff Tendon

Abstract The authors have withdrawn this preprint due to erroneous posting.

scholarly journals Regeneration of a Full-Thickness Defect in Rotator Cuff Tendon with Umbilical Cord-Derived Mesenchymal Stem Cells in a Rat Model

2020 ◽  
Author(s):  
Ji-Hye Yea ◽  
InJa Kim ◽  
Gayoung Sym ◽  
Jin-Kyung Park ◽  
Ah-Young Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Umbilical Cord ◽  
Rat Model ◽  
Orientation Angle ◽  
Saline Group ◽  
Surrounding Tissue ◽  
Full Thickness ◽  
Macroscopic Appearance

AbstractAlthough rotator cuff disease is a common cause of shoulder pain, there is still no treatment method that could halt or reveres its development and progression. The purpose of this study was to investigate the efficacy of umbilical cord-derived mesenchymal stem cells (UC MSCs) on the regeneration of a full-thickness rotator cuff defect (FTD) in a rat model. We injected either UC MSCs or saline to the FTD and investigated macroscopic, histological and biomechanical results and cell trafficking. Treatment with UC MSCs improved macroscopic appearance in terms of tendon thickness at two weeks, and inflammation, defect size, swelling/redness and connection surrounding tissue and slidability at four weeks compared to the saline group. Histologically, UC MSCs induced the tendon matrix formation recovering collagen organization, nuclear aspect ratio and orientation angle of fibroblast as well as suppressing cartilage-related glycosaminoglycan compared to saline group at four weeks. The UC MSCs group also improved ultimate failure load by 25.0% and 19.0% and ultimate stress by 27.3% and 26.8% at two and four weeks compared to saline group. UC MSCs labeled with PKH26 exhibited 5.3% survival at four weeks compared to three hours after injection. This study demonstrated that UC MSCs regenerated the FTD with tendon tissue similar properties to the normal tendon in terms of macroscopic, histological and biomechanical characteristics in a rat model.

scholarly journals Regeneration of a full-thickness defect in rotator cuff tendon with umbilical cord-derived mesenchymal stem cells in a rat model

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0235239
Author(s):  
Ji-Hye Yea ◽  
InJa Kim ◽  
Gayoung Sym ◽  
Jin-Kyung Park ◽  
Ah-Young Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Umbilical Cord ◽  
Rat Model ◽  
Orientation Angle ◽  
Saline Group ◽  
Surrounding Tissue ◽  
Full Thickness ◽  
Macroscopic Appearance

Although rotator cuff disease is a common cause of shoulder pain, there is still no treatment method that could halt or reveres its development and progression. The purpose of this study was to investigate the efficacy of umbilical cord-derived mesenchymal stem cells (UC MSCs) on the regeneration of a full-thickness rotator cuff defect (FTD) in a rat model. We injected either UC MSCs or saline to the FTD and investigated macroscopic, histological and biomechanical results and cell trafficking. Treatment with UC MSCs improved macroscopic appearance in terms of tendon thickness at two weeks, and inflammation, defect size, swelling/redness and connection surrounding tissue and slidability at four weeks compared to the saline group. Histologically, UC MSCs induced the tendon matrix formation recovering collagen organization, nuclear aspect ratio and orientation angle of fibroblast as well as suppressing cartilage-related glycosaminoglycan compared to saline group at four weeks. The UC MSCs group also improved ultimate failure load by 25.0% and 19.0% and ultimate stress by 27.3% and 26.8% at two and four weeks compared to saline group. UC MSCs labeled with PKH26 exhibited 5.3% survival at four weeks compared to three hours after injection. This study demonstrated that UC MSCs regenerated the FTD with tendon tissue similar properties to the normal tendon in terms of macroscopic, histological and biomechanical characteristics in a rat model.

scholarly journals Therapeutic Effects of Umbilical Cord Blood-Derived Mesenchymal Stem Cells Combined with Polydeoxyribonucleotides on Full-Thickness Rotator Cuff Tendon Tear in a Rabbit Model

2018 ◽  
Vol 27 (11) ◽  
pp. 1613-1622 ◽  
Author(s):  
Dong Rak Kwon ◽  
Gi-Young Park ◽  
Yong Suk Moon ◽  
Sang Chul Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Rabbit Model ◽  
Full Thickness ◽  
Tendon Tear ◽  
Rotator Cuff Tendon ◽  
Significant Difference

While therapies using mesenchymal stem cells (MSCs) to treat rotator cuff tendon tear (RCTT) have yielded some promising preliminary results, MSCs therapy has not yet completely regenerated full-thickness RCTT (FTRCTT). It has recently been reported that polydeoxyribonucleotide (PDRN) is effective in the treatment of chronic rotator cuff disease. We hypothesized that local injection of human umbilical cord blood-derived (UCB)–MSCs with PDRN would be more effective in regenerating tendon tear than UCB-MSCs alone. The purpose of this study was to evaluate the effects of UCB–MSCs combined with different doses of PDRN on the regeneration of RCTT in a chronic RCTT model by using a rabbit model. New Zealand white rabbits ( n = 24) with FTRCTT were allocated randomly into three groups (8 rabbits per group). Three different injectants (G1-S, 0.2 mL UCB-MSCs; G2-P1, 0.2 mL UCB-MSCs with one injection of 0.2 mL PDRN; G3-P4, 0.2 mL UCB-MSCs, and four injections of 0.2 mL PDRN per week) were injected into FTRCTT under US-guidance. After the rabbits were euthanized, we evaluated ross morphological and histological change. Motion analysis was also performed. There were significant differences in gross morphological changes between before, and at 4 weeks after injection, in all three groups, but no differences were found among the three groups. Masson’s trichrome (MT) or anti-type 1 collagen antibody (COL-1)-positive cell densities in G2-P1 and G3-P4 were improved significantly compared with those in G1-S, but showed no significant difference between G2-P1 and G3-P4. On motion analysis, walking distance and fast walking time in G2-P1 and G3-P4 were significantly longer/higher than those in G1-S, but showed no significant differences between G2-P1 and G3-P4. These results demonstrated that there was no significant difference in the gross morphologic change of tendon tear between UCB-MSCs only and combination with PDRN injection in rabbit model of chronic traumatic FTRCTT. Furthermore, there were no significant differences in the regenerative effects between high and low doses of (0.8 and 0.2) mL of PDRN.

scholarly journals Regeneration of Full-Thickness Supraspinatus Rotator Cuff Tendon Tear after Treatment with Autologous Mesenchymal Stem Cells

2020 ◽  
Vol 2 (1) ◽  
pp. e25-e30
Author(s):  
Hassan Mubark
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rotator Cuff ◽  
Older Patients ◽  
Successful Outcome ◽  
Full Thickness ◽  
Steroid Injections ◽  
Rotator Cuff Tendon ◽  
The Subject ◽  
Anti Inflammatory

Rotator cuff tear (RCT) is primarily a disease of middle-aged and older patients. Observational data estimated linear increment in the frequency of RCT over time due to the degenerative process. However, a good proportion of tears in older patients are asymptomatic and do not require any intervention. Sport and non-sport Injuries can contribute to RCTs. Many RCTs can be treated non-surgically with anti-inflammatory medication, steroid injections, and physical therapy for symptomatic relief and to restore shoulder strength and function. Rotator cuff tendon tears have limited ability to heal on their own and most often surgical repair is recommended in people failing non-operative therapy. The recovery time after surgery can be a lengthy process. There are no conclusive data to support the routine use of biologic therapy like mesenchymal stem cells (MSCs) or platelet-rich plasma (PRP) in the treatment of symptomatic RCTs. Herein we report a full-thickness supraspinatus tear (SST) in an elderly patient’s shoulder following three injuries. The tear was confirmed by ultrasound scan (USS) and magnetic resonance imaging (MRI) with SST of 9 mm in length and 13 mm in width which was unresponsive to anti-inflammatory medicines, rehabilitation and steroid injections. The subject, however, did have a definitive clinical and radiological response to a single therapeutic injection using autologous adipose tissue-derived MSCs combined with PRP, the injections were performed by ultrasound guidance into the subacromial bursa, supraspinatus tendon and tendon insertion respectively. After five months an USS showed some healing of the SST. Eight months post-MSC therapy the subject had significant improvement in symptoms, and dramatic improvement of the Disability of the Arm, Shoulder and Hand (DASH) score from baseline of 88.3 prior to the therapy to 16.3 at the final visit. Follow-up MRI scan revealed complete healing of the SST indicating the possible successful outcome of MSC therapy as an alternative non-surgical treatment.

scholarly journals Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Lan ◽  
Fang Liu ◽  
Lixian Chang ◽  
Lipeng Liu ◽  
Yingchi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aplastic Anemia ◽  
Umbilical Cord ◽  
Pediatric Patients ◽  
Statistical Significance ◽  
Severe Aplastic Anemia ◽  
Control Group ◽  
Open Label ◽  
Cell Counts

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).

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