scholarly journals Treatment of Full-Thickness Rotator Cuff Tendon Tear Using Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Polydeoxyribonucleotides in a Rabbit Model

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Rak Kwon ◽  
Gi-Young Park ◽  
Sang Chul Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Motion Analysis ◽  
Rabbit Model ◽  
Full Thickness ◽  
Tendon Tear ◽  
Rotator Cuff Tendon ◽  
Proliferating Cell ◽  
Tear Size

Objective. The aim of this study was to investigate regenerative effects of ultrasound- (US-) guided injection with human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and/or polydeoxyribonucleotide (PDRN) injection in a chronic traumatic full-thickness rotator cuff tendon tear (FTRCTT) in a rabbit model. Methods. Rabbits (n=32) were allocated into 4 groups. After a 5 mm sized FTRCTT just proximal to the insertion site on the subscapularis tendon was created by excision, the wound was immediately covered by a silicone tube to prevent natural healing. After 6 weeks, 4 injectants (0.2 mL normal saline, G1-SAL; 0.2 mL PDRN, G2-PDRN; 0.2 mL UCB-MSCs, G3-MSC; and 0.2 mL UCB-MSCs with 0.2 ml PDRN, G4-MSC + PDRN) were injected into the FTRCTT under US guidance. We evaluated gross morphologic changes on all rabbits after sacrifice. Masson’s trichrome, anti-type 1 collagen antibody, bromodeoxyuridine, proliferating cell nuclear antigen, vascular endothelial growth factor, and platelet endothelial cell adhesion molecule stain were performed to evaluate histological changes. Motion analysis was also performed. Results. The gross morphologic mean tendon tear size in G3-MSC and G4-MSC + PDRN was significantly smaller than that in G1-SAL and G2-PDRN (p<0.05). However, there were no significant differences in the tendon tear size between G3-MSC and G4-MSC + PDRN. In G4-MSC + PDRN, newly regenerated collagen type 1 fibers, proliferating cell activity, angiogenesis, walking distance, fast walking time, and mean walking speed were greater than those in the other three groups on histological examination and motion analysis. Conclusions. Coinjection of UCB-MSCs and PDRN was more effective than UCB-MSC injection alone in histological and motion analysis in a rabbit model of chronic traumatic FTRCTT. However, there was no significant difference in gross morphologic change of tendon tear between UCB-MSCs with/without PDRN injection. The results of this study regarding the combination of UCB-MSCs and PDRN are worth additional investigations.

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.

Regenerative effects of mesenchymal stem cells by dosage in a chronic rotator cuff tendon tear in a rabbit model

2019 ◽  
Vol 14 (11) ◽  
pp. 1001-1012
Author(s):  
Dong Rak Kwon ◽  
Gi-Young Park ◽  
Sang Chul Lee
Keyword(s):  
Rotator Cuff ◽  
Motion Analysis ◽  
Rabbit Model ◽  
Optimal Dose ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Full Thickness ◽  
Tendon Tear ◽  
Rotator Cuff Tendon

Aim: We investigated the therapeutic effects and optimal dose of human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection in a chronic full-thickness rotator cuff tendon tear. Methods: Rabbits (n = 30) were allocated into three groups (normal saline, G1-Sal; 1 × 106 cells UCB-MSC, G2-Low; 2 × 106 cells UCB-MSC, G3-High). Injections were done into the chronic full-thickness rotator cuff tendon tear 6 weeks after a full-thickness tendon tear of the subscapularis was created. Gross & histologic evaluation and motion analysis was done at pre and 4 weeks post-injection. Results: There were no significant differences in tear size and motion analysis parameters 4 weeks after injection between G2-Low and G3-High. Conclusion: The benefits of UCB-MSCs are not dose-dependent in a rabbit 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 ◽  
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 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 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.

A 3-Dimensional Bioprinted Scaffold With Human Umbilical Cord Blood–Mesenchymal Stem Cells Improves Regeneration of Chronic Full-Thickness Rotator Cuff Tear in a Rabbit Model

2020 ◽  
Vol 48 (4) ◽  
pp. 947-958 ◽  
Author(s):  
Dong Rak Kwon ◽  
Seungman Jung ◽  
Jinah Jang ◽  
Gi-Young Park ◽  
Yong Suk Moon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rotator Cuff ◽  
Surgical Repair ◽  
Rabbit Model ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Full Thickness ◽  
3 Dimensional ◽  
Cuff Tear ◽  
Tear Size

Background: Chronic full-thickness rotator cuff tears (FTRCTs) represent a major clinical concern because they show highly compromised healing capacity. Purpose: To evaluate the efficacy of using a 3-dimensional (3D) bioprinted scaffold with human umbilical cord blood (hUCB)–mesenchymal stem cells (MSCs) for regeneration of chronic FTRCTs in a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 32 rabbits were randomly assigned to 4 treatment groups (n = 8 per group) at 6 weeks after a 5-mm FTRCT was created on the supraspinatus tendon. Group 1 (G1-SAL) was transplanted with normal saline. Group 2 (G2-MSC) was transplanted with hUCB-MSCs (0.2 mL, 1 × 106) into FTRCTs. Group 3 (G3-3D) was transplanted with a 3D bioprinted construct without MSCs, and group 4 (G4-3D+MSC) was transplanted with a 3D bioprinted construct containing hUCB-MSCs (0.2 mL, 1 × 106 cells) into FTRCTs. All 32 rabbits were euthanized at 4 weeks after treatment. Examination of gross morphologic changes and histologic results was performed on all rabbits after sacrifice. Motion analysis was also performed before and after treatment. Results: In G4-3D+MSC, newly regenerated collagen type 1 fibers, walking distance, fast walking time, and mean walking speed were greater than those in G2-MSC based on histochemical and motion analyses. In addition, when compared with G3-3D, G4-3D+MSC showed more prominent regenerated tendon fibers and better parameters of motion analysis. However, there was no significant difference in gross tear size among G2-MSC, G3-3D, and G4-3D+MSC, although these groups showed significant decreases in tear size as compared with the control group (G1-SAL). Conclusion: Findings of this study show that a tissue engineering strategy based on a 3D bioprinted scaffold filled with hUCB-MSCs can improve the microenvironment for regenerative processes of FTRCT without any surgical repair. Clinical Relevance: In the case of rotator cuff tear, the cell loss of the external MSCs can be increased by exposure to synovial fluid. Therefore, a 3D bioprinted scaffold in combination with MSCs without surgical repair may be effective in increasing cell retention in FTRCT.

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