Expanded adipose derived mesenchymal stromal cells are effective in treating chronic insertional patellar tendinopathy: clinical and MRI evaluations of a pilot study.

PURPOSE: Effect of ultrasound guided injections of autologous ASCs in chronic recalcitrant patellar tendinopathy. METHODS: Fourteen patients (16 knees, 12/2 males/females) with chronic, recalcitrant (unsuccessfully treated with nonoperative treatments) insertional PT underwent clinical evaluation and magnetic resonance imaging (MRI) before intervention. Stromal vascular fraction cells (SVF) were expanded by in-vitro culture and characterized by flow cytometry. Players were injected with three bi-weekly injections of ASCs followed by physiotherapy. They underwent serial clinical evaluations during a 12-month period with repeated MRI at 6-month post-injection. RESULTS: Victorian Institute of sports assessment-patellar tendon questionnaire (VISA-P) scores improved from 43.8 ± 4.9 at baseline to 58.1 ± 7.1, 70.3 ± 7.9 and 78.7 ± 7.5 at 3, 6, and12months follow-up, respectively. (p = 0.0004 comparing each variable with the previous one). Mean Visual analogue pain in sports (VAS-sport) score during practice significantly decreased from 7.4 ± 0.5 at baseline to 5.2 ± 1.5 9 (p = 0.0005), 3.3 ± 1.1 (p = 0.0004) and 1.5 ± 0.7 (P = 0.0004) at 3, 6, and 12 months, respectively. Mean Tegner-scores for patients were 8.0 ± 0.8 before injury and 2.3 ± 0.9 before treatment, thereafter, improving to 4.8 ± 0.8 and 7.2 ± 0.7 at 6- and 12- months, respectively (p = 0.0001). MRI assessed tendon width' did not change over the first 6 months post-intervention. Significant changes were observed for: tendon thickness (12.8 ± 1.1 to 10.9 ± 0.7, P = 0.0001); tear length (9.3 ± 1.3 to 2.3 ± 0.7, P = 0.0001), tear width (6.3 ± 0.8 to 3.4 ± 0.4, P = 0.0001), and tear thickness (4.6 ± 0.4 to 2.6 ± 0., P = 0.0001) at baseline and 6 months, respectively. CONCLUSION: Patients with recalcitrant insertional PT showed significant clinical improvement and structural repair at the patellar insertional tendinopathy after injections of autologous ASCs. Results of this study are promising and open a new biological therapeutic modality to treat PT.

Promising improvement of chronic lateral elbow tendinopathy by using adipose derived mesenchymal stromal cells: a pilot study.

PURPOSE: Study the effect of Adipose derived stromal cells (ASCs) injection as therapeutic procedure on the common extensor tendinopathy. METHODS: Eighteen Tennis players with chronic, recalcitrant LET (who have previously been unsuccessfully treated with nonoperative treatments) underwent clinical evaluation and magnetic resonance imaging (MRI) before intervention. Stromal vascular fraction cells (SVF) were expanded by in vitro culture and ASCs were obtained and characterized by flow cytometry. ASCs were injected into the site of tendinopathy (identified by ultrasound imaging at the origin of the common extensor tendon) on a single occasion followed by physiotherapy. Players underwent serial clinical evaluations during a 12-month period and repeated MRI at 6-month post-injection. RESULTS: At 6-month clinical evaluation revealed significant improvements compared to baseline in mean Visual Analog Scale (VAS) scores for: (1) maximum pain score (from 6.28 ± 1.65, to 1.0 ± 0.43; p < .001); (2) Mean quick Disabilities of the Arm, Shoulder and Hand (QuickDASH-Compulsory score: 51.38 ± 12.02 to 12.33 ± 4.66; p < .001); (3) QuickDASH-Sport score: 56.94 ± 15.44 to 8.68 ± 8.86; p < .001). Validated MRI scoring system grade of tendinopathy also improved significantly: 4.22 ± 0.26 to 2.22 ± 0.10 (p < .001). At 12-month from injection, VAS maximun pain score further decreased to 0.74 ± 0.44 (p < .001) and QuickDASH-Compulsory score to 5.56 ± 3.58 (p < .001). Average time to return to play tennis was 3,31 ± 0,61 month post-intervention. CONCLUSION: Tennis players with recalcitrant LET showed significant clinical improvement and structural repair at the origin of the common tendon origin after injection of autologous ASCs. Results of this study are promising and open a new biological therapeutic modality to treat LET. Even if the results of this pilot study are positive, future well-designed studies, i.e. prospective randomized trials are needed to define the role of cell therapy in treating LET.

Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions.

PURPOSE: To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT. METHODS: Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed. RESULTS: Both regions examined, IR and UIR, exhibited over weeks 1-17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR. CONCLUSION: This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture.

Clinical and Structural Evaluations of Rotator Cuff Repair With and Without Added Platelet-Rich Plasma at 5-Year Follow-up: A Prospective Randomized Study.

BACKGROUND: Platelet-rich plasma (PRP) has been studied with the objective of reducing the retear rate and improving functional outcomes after rotator cuff repair. Only one study to date has reported its midterm effect. HYPOTHESIS: PRP promotes better functional and structural results in arthroscopic rotator cuff repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: All patients underwent arthroscopic single-row repair of small to medium supraspinatus tears. At the end of the surgical procedure, liquid PRP prepared by apheresis with autologous thrombin was applied in the tendon-to-bone interface in the PRP group. The outcomes were assessed by the University of California, Los Angeles (UCLA) and Constant scales and the visual analog scale (VAS) for pain at 6, 12, 24, and 60 months after surgery and magnetic resonance imaging at 12 and 60 months. RESULTS: Of 54 patients initially randomized, we analyzed the clinical outcomes in 51 (25 control, 26 PRP) and the structural outcomes in 44 (22 each group). At 60-month follow-up, the mean UCLA scores were 32.5 ± 3.8 and 32.1 ± 4.6 in the control and PRP groups, respectively ( P = .992). The mean Constant scores were 82.0 ± 9.5 in the control group and 82.1 ± 11.0 in the PRP group ( P = .699). The mean VAS scores were 1.4 ± 1.8 and 1.5 ± 2.1 in the control and PRP groups, respectively ( P = .910). None of the clinical assessments at 6, 12, and 24 months in either group produced statistically significant differences, and both groups showed significant improvements throughout the follow-up time in the 3 evaluations ( P < .001). The control group exhibited 1 full-thickness retear (Sugaya type IV) and 11 partial-thickness retears (Sugaya type III), while the PRP group had 7 partial-thickness retears (Sugaya type III). The overall number of retears did not differ between groups ( P = .203). CONCLUSION: PRP obtained by apheresis and applied in liquid form with the addition of thrombin at the end of single-row repair of supraspinatus tears did not promote better clinical or structural results at 60-month follow-up. REGISTRATION: NCT01029574 ( ClinicalTrials.gov identifier).

Laserterapia Para Tratamento De Tendinopatia Induzida Em Ratos Wistar: Estudo Histomorfométrico / Laser Therapy For Treatment Of Tendinopathy Induced In Wistar Rats: An Histomorfometric Study / Terapia Con Láser Para Tratamiento De Tendinopatia Inducida En Ratas Wistar: Estudio Histomorfométrico

O objetivo desse estudo foi avaliar os efeitos da laserterapia na lesão do tendão calcanear comum de ratos Wistar. Foram utilizados 12 ratos machos adultos, distribuídos aleatoriamente em dois grupos (L=laser e C=controle). Todos foram submetidos à tendinopatia unilateral (escolha aleatória) mediante compressão transversal do tendão (10 segundos) com pinça Halstead mosquito, assim como escarificações (com bisturi). Após 24 horas da indução da lesão os animais do grupo L receberam laser (904 nm/3 J/cm²/9s) por 20 dias. Os do grupo C foram manipulados como se fossem receber a radiação. Após 3, 7, 14 e 21 dias da realização da lesão, três ratos de cada grupo foram submetidos à eutanásia, e os tendões obtidos para análise histomorfométrica. As amostras foram processadas como de rotina e os fragmentos corados com hematoxilina-eosina, tricrômico de Masson e Picrosirius Red. Os dados foram analisados por ANOVA, a 5% de probabilidade e análise de regressão. Não houve diferença entre grupos nem entre tempos para as características hemorragia, angiogênese, espessamento do epitendão. Independente do tratamento ocorreu diminuição (p=0,0129) da formação de aderência fibrinosa (do 3o ao 21o dias). Por outro lado, a avaliação morfométrica revelou maiores (p=0,0120) quantidades de fibroblastos no grupo que recebeu laserterapia, não havendo efeito de tempo. Avaliação semiquantitativa, revelou maiores (p=0,0000) quantidades de fibroblastos no grupo tratado, porém nessa análise, a quantidade dessas células aumentou com o tempo (p=0,0001) em ambos os grupos. Diferentemente, ANOVA revelou redução do infiltrado inflamatório do 3o ao 21o dia em ambos os grupos (histologia: p=0,0003; morfometria: p=0,0000).(AU)

The aim of this study was to evaluate the effects of laser therapy in tendinopathy of Achilles tendon of Wistar rats. Thus, 12 adult male rats which were divided into two groups (L=laser and C=control) were used. All animals were submitted to unilateral tendinopathy (random selection) by transverse compression of the tendon (10 seconds) with Halsted forceps, as well as 10 scarifications (using a scalpel). After 24 hours of induction of lesion all animals of Group L received laser (904 nm/3 J/cm²/ 9 s) for 20 days, while Group C were handled as if they would receive radiation. After 3, 7, 14 and 21 days lesion induction, three rats from each group were euthanized, and the tendons obtained for histomorphometric analysis. The samples were processed as routine and the sections stained with hematoxylin-eosin, Masson's trichrome and Picrosirius Red. Data were analyzed by ANOVA, at 5% probability and regression analysis. No differences between groups neither between time for hemorrhage characteristics, angiogenesis, thickening of epitendon. Independently of the treatment there was a decrease (p=0.0129) of fibrinous adhesion (3rd to 21st day). On the other hand, morphometric analysis revealed higher (p=0.0120) amounts of fibroblasts cells in the group receiving laser therapy, with no effect of time. Semiquantitative assessment also showed higher (p=0.0000) amounts of fibroblasts cells in the treated group, but in this analysis, the number of fibroblasts increased with time (p=0.0001) in both group. In contrast, ANOVA revealed a reduction of the inflammatory cells from 3rd to 21st day in both groups (histology: p=0.0003; morphometry: p=0.0000).(AU)

La finalidad de ese estudio fue evaluar los efectos del láser en la lesión del tendón calcáneo común de ratas Wistar. Fueron utilizadas 12 ratas machos adultos, distribuidos al azar en dos grupos (L=láser y C=control). Todos fueron sometidos a tendinopatía unilateral (selección aleatoria) por la compresión transversal del tendón (10 segundos) con una pinza Halstead-Mosquito, y escarificación (con bisturí). Después de 24 horas de la inducción de la lesión los animales del grupo L recibieron láser (904 nm/3J/ cm²/9s) durante 20 días. Los tendones del grupo C fueran manejados como si recibera la radiación. Después de 3, 7, 14 y 21 días de realización de la lesión, tres ratas de cada grupo fueron sacrificadas, y los tendones obtenidos para análisis histomorfométrico. Las muestras fueron procesadas como de rutina y los fragmentos se tiñeron con hematoxilina-eosina, tricrómico de Masson y Picrosirius Red. Los datos fueron analizados por ANOVA, con una probabilidad de 5%, además de análisis de regresión. No hubo diferencias entre los grupos o tiempos para las variables hemorragia, angiogénesis, engrosamiento del epitendón. Independientemente del tratamiento se redujo (p=0,0129) la formación de adherencia fibrinosa (del 3o al 21o días). Por otra parte, la evaluación morfométrica mostró cantidades más altas (p=0,0120) de los fibroblastos en el grupo que recibió el tratamiento con láser, sin efecto del tiempo. Evaluación semicuantitativa reveló mayor (p=0,0000) cantidad de fibroblastos en el grupo tratado, pero en esa análisis la cantidad de esas células aumentó con el tiempo (p=0,0001) en ambos grupos. En contraste, ANOVA reveló reducción del infiltrado inflamatorio entre el 3o y el 21o días, en ambos grupos (histología: p=0,0003; morfometría: p=0,0000). Aunque no hubo diferencias entre grupos en la cantidad de fibras de colágeno (I y III), la morfometría reveló que las ratas del grupo L presentaram mayores cantidades (p=0,0096) de fibras de colágeno.(AU)

Laserterapia Para Tratamento De Tendinopatia Induzida Em Ratos Wistar: Estudo Histomorfométrico / Laser Therapy For Treatment Of Tendinopathy Induced In Wistar Rats: An Histomorfometric Study / Terapia Con Láser Para Tratamiento De Tendinopatia Inducida En Ratas Wistar: Estudio Histomorfométrico

O objetivo desse estudo foi avaliar os efeitos da laserterapia na lesão do tendão calcanear comum de ratos Wistar. Foram utilizados 12 ratos machos adultos, distribuídos aleatoriamente em dois grupos (L=laser e C=controle). Todos foram submetidos à tendinopatia unilateral (escolha aleatória) mediante compressão transversal do tendão (10 segundos) com pinça Halstead mosquito, assim como escarificações (com bisturi). Após 24 horas da indução da lesão os animais do grupo L receberam laser (904 nm/3 J/cm²/9s) por 20 dias. Os do grupo C foram manipulados como se fossem receber a radiação. Após 3, 7, 14 e 21 dias da realização da lesão, três ratos de cada grupo foram submetidos à eutanásia, e os tendões obtidos para análise histomorfométrica. As amostras foram processadas como de rotina e os fragmentos corados com hematoxilina-eosina, tricrômico de Masson e Picrosirius Red. Os dados foram analisados por ANOVA, a 5% de probabilidade e análise de regressão. Não houve diferença entre grupos nem entre tempos para as características hemorragia, angiogênese, espessamento do epitendão. Independente do tratamento ocorreu diminuição (p=0,0129) da formação de aderência fibrinosa (do 3o ao 21o dias). Por outro lado, a avaliação morfométrica revelou maiores (p=0,0120) quantidades de fibroblastos no grupo que recebeu laserterapia, não havendo efeito de tempo. Avaliação semiquantitativa, revelou maiores (p=0,0000) quantidades de fibroblastos no grupo tratado, porém nessa análise, a quantidade dessas células aumentou com o tempo (p=0,0001) em ambos os grupos. Diferentemente, ANOVA revelou redução do infiltrado inflamatório do 3o ao 21o dia em ambos os grupos (histologia: p=0,0003; morfometria: p=0,0000).

The aim of this study was to evaluate the effects of laser therapy in tendinopathy of Achilles tendon of Wistar rats. Thus, 12 adult male rats which were divided into two groups (L=laser and C=control) were used. All animals were submitted to unilateral tendinopathy (random selection) by transverse compression of the tendon (10 seconds) with Halsted forceps, as well as 10 scarifications (using a scalpel). After 24 hours of induction of lesion all animals of Group L received laser (904 nm/3 J/cm²/ 9 s) for 20 days, while Group C were handled as if they would receive radiation. After 3, 7, 14 and 21 days lesion induction, three rats from each group were euthanized, and the tendons obtained for histomorphometric analysis. The samples were processed as routine and the sections stained with hematoxylin-eosin, Masson's trichrome and Picrosirius Red. Data were analyzed by ANOVA, at 5% probability and regression analysis. No differences between groups neither between time for hemorrhage characteristics, angiogenesis, thickening of epitendon. Independently of the treatment there was a decrease (p=0.0129) of fibrinous adhesion (3rd to 21st day). On the other hand, morphometric analysis revealed higher (p=0.0120) amounts of fibroblasts cells in the group receiving laser therapy, with no effect of time. Semiquantitative assessment also showed higher (p=0.0000) amounts of fibroblasts cells in the treated group, but in this analysis, the number of fibroblasts increased with time (p=0.0001) in both group. In contrast, ANOVA revealed a reduction of the inflammatory cells from 3rd to 21st day in both groups (histology: p=0.0003; morphometry: p=0.0000).

La finalidad de ese estudio fue evaluar los efectos del láser en la lesión del tendón calcáneo común de ratas Wistar. Fueron utilizadas 12 ratas machos adultos, distribuidos al azar en dos grupos (L=láser y C=control). Todos fueron sometidos a tendinopatía unilateral (selección aleatoria) por la compresión transversal del tendón (10 segundos) con una pinza Halstead-Mosquito, y escarificación (con bisturí). Después de 24 horas de la inducción de la lesión los animales del grupo L recibieron láser (904 nm/3J/ cm²/9s) durante 20 días. Los tendones del grupo C fueran manejados como si recibera la radiación. Después de 3, 7, 14 y 21 días de realización de la lesión, tres ratas de cada grupo fueron sacrificadas, y los tendones obtenidos para análisis histomorfométrico. Las muestras fueron procesadas como de rutina y los fragmentos se tiñeron con hematoxilina-eosina, tricrómico de Masson y Picrosirius Red. Los datos fueron analizados por ANOVA, con una probabilidad de 5%, además de análisis de regresión. No hubo diferencias entre los grupos o tiempos para las variables hemorragia, angiogénesis, engrosamiento del epitendón. Independientemente del tratamiento se redujo (p=0,0129) la formación de adherencia fibrinosa (del 3o al 21o días). Por otra parte, la evaluación morfométrica mostró cantidades más altas (p=0,0120) de los fibroblastos en el grupo que recibió el tratamiento con láser, sin efecto del tiempo. Evaluación semicuantitativa reveló mayor (p=0,0000) cantidad de fibroblastos en el grupo tratado, pero en esa análisis la cantidad de esas células aumentó con el tiempo (p=0,0001) en ambos grupos. En contraste, ANOVA reveló reducción del infiltrado inflamatorio entre el 3o y el 21o días, en ambos grupos (histología: p=0,0003; morfometría: p=0,0000). Aunque no hubo diferencias entre grupos en la cantidad de fibras de colágeno (I y III), la morfometría reveló que las ratas del grupo L presentaram mayores cantidades (p=0,0096) de fibras de colágeno.