Augmentation of chronic rotator cuff healing using adipose‐derived stem cell‐seeded human tendon‐derived hydrogel

Kaizawa, Yukitoshi; Franklin, Austin; Leyden, Jacinta; Behn, Anthony W.; Tulu, U.S.; Leon, Daniel Sotelo; Wang, Zhen; Abrams, Geoffrey D.; Chang, James; Fox, Paige M.

doi:10.1002/jor.24250

Cited by 40 publications

(40 citation statements)

References 44 publications

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“…On a histological evaluation, fibrocartilage formation is known to play an important role in force transmission and energy dissipation between the 2 tissues of the tendon-to-bone interface enthesis, and fibrocartilage formation is a condition for successful tendon-to-bone interface healing. 15,16,35 In our study, HE and safranin O staining showed excellent results in the cell sheet transplantation after repair group compared with those in the other groups. Additionally, it was confirmed by histomorphological analysis that the ADSC sheet showed excellent results in fibrocartilage formation of tendon-to-bone interface healing.…”

Section: Discussionsupporting

confidence: 61%

“…Previous studies have used adult stem cells, such as bone marrow, adipose, tendon, and cord blood stem cells, to treat tendon diseases. 15,31,33,44 Most studies showed the efficacy of stem cells, but there were some limitations. The most controversial point is that almost all studies have shown the effect of a single stem cell injection; thus, it is unknown how long the stem cells will remain at the repair or application site after the injection.…”

Section: Discussionmentioning

confidence: 99%

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Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

et al. 2020

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Background: Efforts are being made to treat rotator cuff tears (RCTs) that exhibit poor healing and high retear rates. Tendon-to-bone healing using mesenchymal stem cells is being explored, but research is needed to establish effective delivery options. Purpose: To evaluate the effects of an adipose-derived stem cell (ADSC) sheet on mesenchymal stem cell delivery for tendon-to-bone healing of a chronic RCT in rats and to demonstrate that ADSC sheets enhance tendon-to-bone healing. Study Design: Controlled laboratory study. Methods: Mesenchymal stem cells were obtained from rat adipose tissue, and a cell sheet was prepared using a temperature-responsive dish. To evaluate the efficacy of stem cells produced in a sheet for the lesion, the experiment was conducted with 3 groups: repair group, cell sheet transplantation after repair group, and cell sheet–only group. Histological, biomechanical, and micro–computed tomography (micro-CT) results were compared among the groups. Results: Hematoxylin and eosin staining for histomorphological analysis revealed that the cell sheet transplantation after repair group (5.75 ± 0.95) showed statistically significant higher scores than the repair (2.75 ± 0.50) and cell sheet–only (3.25 ± 0.50) groups ( P < .001). On safranin O staining, the cell sheet transplantation after repair group (0.51 ± 0.04 mm2) had a larger fibrocartilage area than the repair (0.31 ± 0.06 mm2) and cell sheet–only (0.32 ± 0.03 mm2) groups ( P = .001). On micro-CT, bone volume/total volume values were significantly higher in the cell sheet transplantation after repair group (23.98% ± 1.75%) than in the other groups ( P < .039); there was no significant difference in the other values. On the biomechanical test, the cell sheet transplantation after repair group (4 weeks after repair) showed significantly higher results than the other groups ( P < .005). Conclusion: Our study shows that engineered stem cells are a clinically feasible stem cell delivery tool for rotator cuff repair. Clinical Relevance: This laboratory study provides evidence that ADSCs are effective in repairing RCTs, which are common sports injuries.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

et al. 2020

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“…Nevertheless, it was noted that an ASCs' application decreased migration and proliferation of inflammatory cells, promoted the expression of anti-inflammatory cells, and downregulated the synthesis of proinflammatory cytokines, in laboratory models [70,71] The regenerative properties of ASCs have also been examined in rotator cuff repair models [72][73][74][75][76]. It has been noted that the local application of ASCs could result in less pronounced inflammation and increased bone mineral density in histologically evaluated tissues or improved their biomechanical function [72][73][74]. However, others have reported that the subjects treated with ASCs did not benefit from its application as compared with a control group [75,76].…”

Section: Animal Modelsmentioning

confidence: 99%

“…Augmentation of chronic rotator cuff healing using adipose-derived stem cell-seeded human tendon-derived hydrogel [73] Controlled experimental study…”

Section: Animal Modelsmentioning

confidence: 99%

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Jankowski

Dompe

Sibiak

et al. 2020

Cells

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Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

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“…Several animal models have demonstrated cell-based approaches using MSCs can improve tendon repair, and when these studies are taken together, they improved histological and biomechanical properties of the tendons, indicating an increased rate of tendon healing and maturation [25,26]. BMC and autologous-derived stem cells have also been used in the surgical management of rotator cuff repair to augment healing [22,[27][28][29].…”

Section: Introductionmentioning

confidence: 99%

A Randomized Controlled Trial of the Treatment of Rotator Cuff Tears with Bone Marrow Concentrate and Platelet Products Compared to Exercise Therapy: A Midterm Analysis

Centeno

Fausel

Stemper³

et al. 2020

Stem Cells International

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Injectable regenerative therapies such as bone marrow concentrate (BMC) and platelet-rich plasma (PRP) may represent a safe alternative in the treatment of rotator cuff tears. This is a midterm review of a randomized, crossover trial comparing autologous BMC and platelet product injections versus exercise therapy in the treatment of partial and full-thickness supraspinatus tears. Patients enrolled into the study were between 18 and 65 years of age presenting to an outpatient orthopedic clinic with partial to full thickness, nonretracted supraspinatus tendon tears. Enrolled patients were randomized to either ultrasound-guided autologous BMC with PRP and platelet lysate (PL) percutaneous injection treatment or exercise therapy. Patients could cross over to BMC treatment after at least 3 months of exercise therapy. Patients completed the Disability of the Arm, Shoulder and Hand (DASH) scores as the primary outcome measure. Secondary outcomes included the numeric pain scale (NPS), a modified Single Assessment Numeric Evaluation (SANE), and a blinded MRI review. At this midterm review, results from 25 enrolled patients who have reached at least 12-month follow-up are presented. No serious adverse events were reported. Significant differences were seen in patient reported outcomes for the BMC treatment compared to exercise therapy at 3 and 6 months for pain, and for function and reported improvement (SANE) at 3 months (p<.05). Patients reported a mean 89% improvement at 24 months, with sustained functional gains and pain reduction. MRI review showed a size decrease of most tears post-BMC treatment. These findings suggest that ultrasound-guided BMC and platelet product injections are a safe and useful alternative to conservative exercise therapy of torn, nonretracted supraspinatus tendons. This trial is registered with NCT01788683.

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Augmentation of chronic rotator cuff healing using adipose‐derived stem cell‐seeded human tendon‐derived hydrogel

Cited by 40 publications

References 44 publications

Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

A Randomized Controlled Trial of the Treatment of Rotator Cuff Tears with Bone Marrow Concentrate and Platelet Products Compared to Exercise Therapy: A Midterm Analysis

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