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Journal ArticleDOI

Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells

TL;DR: Implantation of BMMC in rotator cuff sutures appears to be a safe and promising alternative to other biological approaches currently used to enhance tissue quality in affected tendons.
Abstract: Purpose To investigate the behavior of rotator cuff tears treated with conventional repair technique with the aid of autologous bone marrow mononuclear cells (BMMC).
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Journal ArticleDOI
TL;DR: This review describes and critically assess the current strategies for enhancing tendon repair by biological means, mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage.

478 citations


Cites background from "Conventional rotator cuff repair co..."

  • ...Only one patient had deterioration of tendon strength and pain after 1 year [127]....

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Journal ArticleDOI
TL;DR: In this article, two case studies were presented to demonstrate that children who experience trauma-related nightmares may benefit from cognitive-behavioral therapy for this sleep problem, adapted from the empirically supported adult treatment for chronic trauma related night-mares: exposure, relaxation, and rescripting therapy (ERRT).
Abstract: Two case studies are presented to demonstrate that children who experience trauma-related nightmares may benefit from cognitive-behavioral therapy for this sleep problem. The treatment was adapted from the empirically supported adult treatment for chronic trauma-related night- mares: exposure, relaxation, and rescripting therapy (ERRT). Pretreatment and posttreatment nightmare frequency and severity were measured in addition to subjective nightmare-related distress, behavioral problems, sleep quality and quantity, and symptoms of posttraumatic stress disorder (PTSD), anxiety, and depression. Improvement in nightmare and sleep disturbance fre- quencies were found as well as reductions in parents' reports of child behavior problems. This study provides preliminary support for the use of ERRT with children.

448 citations

Journal ArticleDOI
TL;DR: The results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.
Abstract: The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface. Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up MRI (minimum ten-year follow-up). Bone marrow-derived MSC injection as an adjunctive therapy during rotator cuff repair enhanced the healing rate and improved the quality of the repaired surface as determined by ultrasound and MRI. Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months. Bone marrow concentrate (BMC) injection also prevented further ruptures during the next ten years. At the most recent follow-up of ten years, intact rotator cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but just 20 (44 %) of the 45 patients in the control group. The number of transplanted MSCs was determined to be the most relevant to the outcome in the study group, since patients with a loss of tendon integrity at any time up to the ten-year follow-up milestone received fewer MSCs as compared with those who had maintained a successful repair during the same interval. This study showed that significant improvement in healing outcomes could be achieved by the use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff repair. Furthermore, our study showed a substantial improvement in the level of tendon integrity present at the ten-year milestone between the MSC-treated group and the control patients. These results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.

303 citations


Cites background from "Conventional rotator cuff repair co..."

  • ...In another human clinical study [11] that was begun ten years after our study, the authors were able to enroll 14 patients in a short time with complete RC tears repaired with transosseous stitches through miniopen incisions....

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Journal ArticleDOI
TL;DR: Use of growth factors, stem cell therapy, and other tissue-engineering means serve to augment classical surgical rotator cuff repair procedures, reflecting paucity of research in this field.

124 citations


Cites methods from "Conventional rotator cuff repair co..."

  • ...Prior to cuff repairs, autologous BMMCs were harvested from the iliac crest and subsequently injected into the repaired tendon borders.(13) The BMMC fractions were obtained by cell sorting and resuspended in saline enriched with 10% autologous serum....

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Journal ArticleDOI
TL;DR: Although still in the early stages of application, MSC augmentation of surgical rotator cuff repair appears useful for providing an adequate biological environment around the repair site.
Abstract: Background:The mesenchymal stem cell (MSC)–based tissue engineering approach has been developed to improve the treatment of rotator cuff tears.Hypothesis/Purpose:The purpose was to determine the ef...

113 citations

References
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Journal ArticleDOI
06 Mar 1998-Science
TL;DR: Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers.
Abstract: Growth and repair of skeletal muscle are normally mediated by the satellite cells that surround muscle fibers. In regenerating muscle, however, the number of myogenic precursors exceeds that of resident satellite cells, implying migration or recruitment of undifferentiated progenitors from other sources. Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers. Genetically modified, marrow-derived myogenic progenitors could potentially be used to target therapeutic genes to muscle tissue, providing an alternative strategy for treatment of muscular dystrophies.

2,881 citations


"Conventional rotator cuff repair co..." refers background in this paper

  • ...[12] were the first to describe the role of adult stem cells in tissue regeneration....

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  • ...In another experiment, instead of injecting bone marrow cells directly into the muscle injury, immunodeficient mice received a bone marrow transplant [12]....

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Journal ArticleDOI
TL;DR: Impingement on the tendinous portion of the rotator cuff by the coraco-acromial ligament and the anterior third of the acromion is responsible for a characteristic syndrome of disability of the shoulder.
Abstract: Impingement on the tendinous portion of the rotator cuff by the coraco-acromial ligament and the anterior third of the acromion is responsible for a characteristic syndrome of disability of the shoulder A characteristic proliferative spur and ridge has been noted on the anterior lip and undersurfac

2,335 citations

Journal ArticleDOI
TL;DR: The minimum twelve-month evaluation showed excellent pain relief and improvement in the ability to perform activities of daily living despite the high rate of recurrent defects; however, at a minimum follow-up of two years, the results deteriorated with only twelve patients who had an American Shoulder and Elbow Surgeons score of >/=80.
Abstract: Background: The impact of a recurrent defect on the outcome after rotator cuff repair has been controversial. The purpose of this study was to evaluate the functional and anatomic results after arthroscopic repair of large and massive rotator cuff tears with use of ultrasound as an imaging modality to determine the postoperative integrity of the repair. Methods: Eighteen patients who had complete arthroscopic repair of a tear measuring >2 cm in the transverse dimension were evaluated at a minimum of twelve months after surgery and again at two years after surgery. The evaluation consisted of a standardized history and physical examination as well as calculation of the preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons. The strength of both shoulders was quantitated postoperatively with use of a portable dynamometer. Ultrasound studies were performed with use of an established and validated protocol at a minimum of twelve months after surgery. Results: Recurrent tears were seen in seventeen of the eighteen patients. Despite the absence of healing at twelve months after surgery, thirteen patients had an American Shoulder and Elbow Surgeons score of ≥90 points. Sixteen patients had an improvement in the functional outcome score, which increased from an average of 48.3 to 84.6 points. Sixteen patients had a decrease in pain, and twelve had no pain. Although eight patients had preoperative forward elevation to <95°, all eighteen regained motion above shoulder level and had an average of 152° of elevation. At the second evaluation, a minimum of twenty-four months after surgery, the average score, according to the system of the American Shoulder and Elbow Surgeons, had decreased to 79.9 points; only nine patients had a score of ≥90 points, and six patients had a score of ≤79 points. The average forward elevation decreased to 142°. Conclusions: Arthroscopic repair of large and massive rotator cuff tears led to a high percentage of recurrent defects. The minimum twelve-month evaluation showed excellent pain relief and improvement in the ability to perform activities of daily living despite the high rate of recurrent defects; however, at a minimum follow-up of two years, the results deteriorated with only twelve patients who had an American Shoulder and Elbow Surgeons score of ≥80. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.

1,871 citations


"Conventional rotator cuff repair co..." refers background in this paper

  • ...According to several authors [4, 9, 14, 22, 28, 37], the 75% threshold of good results is not exceeded in this type of injury....

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Journal ArticleDOI
TL;DR: The method of repair of massive rotator cuff tears yielded a comparatively low retear rate and good-to-excellent clinical results; however, the repair did not result in substantial reversal of muscular atrophy and fatty degeneration.
Abstract: Background: Massive tears of the tendons of the rotator cuff cause atrophy and fatty degeneration of the rotator cuff muscles and painful loss of function of the shoulder. Repair of massive rotator cuff tears is often followed by retears of the tendons, additional muscular degeneration, and a poor clinical outcome. The purposes of this study were to determine whether a new method of repair of rotator cuff tendons can yield a lower retear rate and a better clinical outcome than previously reported methods, to assess the muscular changes following repair of massive tears of the musculotendinous units, and to correlate findings on magnetic resonance imaging with the clinical results. Methods: Twenty-nine massive rotator cuff tears involving complete detachment of at least two tendons were repaired operatively with use of a new laboratory-tested technique in a prospective study. At least two years (average, thirty-seven months; range, twenty-four to sixty-one months) postoperatively, twenty-seven patients were evaluated clinically and with magnetic resonance imaging to determine the clinical outcome, the integrity of the repair, and the condition of the rotator cuff muscles. Results: The age and gender-adjusted Constant score improved from an average of 49 percent preoperatively to an average of 85 percent postoperatively, corresponding to a subjective shoulder value of 78 percent of that of a normal shoulder. Pain-free flexion improved from an average of 92 degrees to an average of 142 degrees, and abduction improved from an average of 82 degrees to an average of 137 degrees. Pain decreased and performance of activities of daily living improved significantly (p < 0.05). The seventeen patients who had a structurally successful repair all had an excellent clinical outcome. Muscle atrophy could not be reversed except in successfully repaired supraspinatus musculotendinous units. Fatty degeneration increased in all muscles. Conclusions: The method of repair of massive rotator cuff tears that was used in this study yielded a comparatively low retear rate and good-to-excellent clinical results; however, the repair did not result in substantial reversal of muscular atrophy and fatty degeneration. Retears occurred more often in patients who had had a shorter interval between the onset of the symptoms and the operation (p < 0.05). Patients who had a retear had improvement of the shoulder compared with the preoperative state, but they had less improvement than did those who had a successful repair.

1,255 citations


"Conventional rotator cuff repair co..." refers background in this paper

  • ...With the advent of arthroscopy, these procedures became increasingly popular and widespread in the orthopedic community, but none of these advances has brought significant improvement to the quality of postoperative results in patients with large rotator cuff injuries: the overall rate of rerupture over the first postoperative year ranges from 25 to 65% depending on lesion extent [15, 22]....

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01 Jan 2005
TL;DR: The scientific and clinical challenge remains: to perfect cell-based tissue-engineering protocols to utilize the body's own rejuvenation capabilities by managing surgical implantations of scaffolds, bioactive factors, and reparative cells to regenerate damaged or diseased skeletal tissues.
Abstract: Adult stem cells provide replacement and repair descendants for normal turnover or injured tissues. These cells have been isolated and expanded in culture, and their use for therapeutic strategies requires technologies not yet perfected. In the 1970s, the embryonic chick limb bud mesenchymal cell culture system provided data on the differentiation of cartilage, bone, and muscle. In the 1980s, we used this limb bud cell system as an assay for the purification of inductive factors in bone. In the 1990s, we used the expertise gained with embryonic mesenchymal progenitor cells in culture to develop the technology for isolating, expanding, and preserving the stem cell capacity of adult bone marrow-derived mesenchymal stem cells (MSCs). The 1990s brought us into the new field of tissue engineering, where we used MSCs with site-specific delivery vehicles to repair cartilage, bone, tendon, marrow stroma, muscle, and other connective tissues. In the beginning of the 21st century, we have made substantial advances: the most important is the development of a cell-coating technology, called painting, that allows us to introduce informational proteins to the outer surface of cells. These paints can serve as targeting addresses to specifically dock MSCs or other reparative cells to unique tissue addresses. The scientific and clinical challenge remains: to perfect cell-based tissue-engineering protocols to utilize the body's own rejuvenation capabilities by managing surgical implantations of scaffolds, bioactive factors, and reparative cells to regenerate damaged or diseased skeletal tissues.

734 citations


"Conventional rotator cuff repair co..." refers background in this paper

  • ...skin, intestine and bone marrow, other tissues and organs— liver, pancreas, skeletal muscle (associated with the locomotor system), adipose tissue and nervous system—have a stock of tissue-specific stem cells albeit with a limited capacity to regenerate after significant injury [2, 6]....

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  • ...A strategy aiming to revitalize the tendon structure through cell therapy [6, 20, 21] is the natural step ahead sought by many centers worldwide, once it would probably overcome this complication by increasing tendon resistance to muscle traction [7, 26, 30, 35]....

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