Regeneration of Tendon-to-Bone Interface of Rotator Cuff with Umbilical Cord Derived Mesenchymal Stem Cells and Gradient Extracellular Matrix Scaffolds from Adipose Tissue in a Rat Model

2020 ◽  
Author(s):  
Ji-Hye Yea ◽  
Tae Soo Bae ◽  
Byoung Jae Kim ◽  
Yong Woo Cho ◽  
Chris Hyunchul Jo
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Rotator Cuff ◽  
Umbilical Cord ◽  
Rat Model ◽  
Bone Interface ◽  
Extracellular Matrix Scaffolds

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 ◽  
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 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 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

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 hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model

2019 ◽  
Vol 28 (12) ◽  
pp. 1552-1559 ◽  
Author(s):  
Jianwei Xu ◽  
Zhanhui Feng ◽  
Xianyao Wang ◽  
Ying Xiong ◽  
Lan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Hypoxic Ischemic Encephalopathy ◽  
Human Umbilical Cord ◽  
Motor Functions ◽  
Ischemic Encephalopathy

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.

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