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com/esps/ World J Stem Cells 2015 May 26; 7(4): 691-699
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 1948-0210 (online)
DOI: 10.4252/wjsc.v7.i4.691 © 2015 Baishideng Publishing Group Inc. All rights reserved.

REVIEW

Stem cell therapy in the management of shoulder rotator
cuff disorders

Maria Valencia Mora, Miguel A Ruiz Ibán, Jorge Díaz Heredia, Raul Barco Laakso, Ricardo Cuéllar,
Mariano García Arranz

Maria Valencia Mora, Miguel A Ruiz Ibán, Jorge Díaz Abstract
Heredia, Unidad de Hombro y Codo, Hospital Universitario
Ramón y Cajal, 28034 Madrid, Spain Rotator cuff tears are frequent shoulder problems that
Raul Barco Laakso, Hospital Universitario La Paz, 28046 are usually dealt with surgical repair. Despite improved
Madrid, Spain surgical techniques, the tendon-to-bone healing rate
Ricardo Cuéllar, Departamento de Traumatología y Cirugía is unsatisfactory due to difficulties in restoring the
Ortopédica, Hospital Universitario Donostia, 20080 San delicate transitional tissue between bone and tendon.
Sebastián, Spain
It is essential to understand the molecular mechanisms
Mariano García Arranz, Instituto de Investigación Sanitaria
Fundación Jiménez Diaz, 28040 Madrid, Spain that determine this failure. The study of the molecular
Mariano García Arranz, Departamento de Cirugía, Universidad environment during embryogenesis and during normal
Autónoma de Madrid, 28049 Madrid, Spain healing after injury is key in devising strategies to get
Author contributions: All authors had contributed to the design, a successful repair. Mesenchymal stem cells (MSC) can
writing and reviewing of this original. differentiate into different mesodermal tissues and have
Conflict-of-interest: Mariano García Arranz has the following a strong paracrine, anti-inflammatory, immunoregulatory
conflict of interest: MGA is inventor on 2 patents entitled
and angiogenic potential. Stem cell therapy is thus a
“Identification and isolation of multipotent cells from non-
osteochondral mesenchymal tissue” (10157355957US) and “Use potentially effective therapy to enhance rotator cuff
of adipose tissue-derived stromal stem cells in treating fistula” healing. Promising results have been reported with the
(US11/167061). The Universidad Autónoma de Madrid (UAM) and use of autologous MSC of different origins in animal
Cellerix share patent rights. The rest of the authors do not have any studies: they have shown to have better healing proper­
conflict of interest. ties, increasing the amount of fibrocartilage formation
Open-Access: This article is an open-access article which was and improving the orientation of fibrocartilage fibers with
selected by an in-house editor and fully peer-reviewed by external
less immunologic response and reduced lymphocyte
reviewers. It is distributed in accordance with the Creative
Commons Attribution Non Commercial (CC BY-NC 4.0) license, infiltration. All these changes lead to an increase in
which permits others to distribute, remix, adapt, build upon this biomechanical strength. However, animal research is still
work non-commercially, and license their derivative works on inconclusive and more experimental studies are needed
different terms, provided the original work is properly cited and before human application. Future directions include
the use is non-commercial. See: http://creativecommons.org/ expanded stem cell therapy in combination with growth
licenses/by-nc/4.0/ factors or different scaffolds as well as new stem cell
Correspondence to: Miguel A Ruiz Ibán, MD, PhD, Unidad types and gene therapy.
de Hombro y Codo, Hospital Universitario Ramón y Cajal, Ctra.
de Colmenar Viejo km. 9, 100, 28034 Madrid,
Spain. drmri@hotmail.com Key words: Rotator cuff; Enthesis; Biologic; Stem cells
Telephone: +34-91-3368000
Fax: +34-91-3368000 © The Author(s) 2015. Published by Baishideng Publishing
Received: September 7, 2014 Group Inc. All rights reserved.
Peer-review started: September 10, 2014
First decision: December 17, 2014 Core tip: Current surgical techniques in rotator cuff
Revised: January 26, 2015
repair do not achieve good tendon-to-bone healing.
Accepted: February 4, 2015
Article in press: February 9, 2015 The use of stem cells to improve healing is a promising
Published online: May 26, 2015 alternative. Different in vivo animal studies have shown

WJSC|www.wjgnet.com 691 May 26, 2015|Volume 7|Issue 4|

IX and X transition zone between the rotator cuff and the collagen fibres have also been detected. 7(4): 691-699 Available from: URL: http://www. Thus. tendon. Stem cell therapy for rotator cuff good results in achieving restoration of the native Table 1 Main biochemical and histological characteristics of enthesis. García Arranz M. Lastly.doi. World J Stem fibrocartilage (small amounts of X) component Cells 2015. Zone 3 is constituted by tendon to bone repair techniques attain only a fibro. [1. In the non-mineralized fibrocartilage repair is probably biologic. the focus in research has changed zone 4 is characterized for a bone-alike composition. IX and X) Laakso R. with a highly specialized vascular scar tissue that has relatively poor mechanical mineralized content and type I collagen fibres. The reparative process can be divided into 3 isolated GF or platelet rich plasma has been recently phases (inflammatory. The fibro vascular tissue that substitutes well as stem cells. ENTHESIS: TENDON TO BONE HEALING Rotator cuff tears often require surgical treatment in order to increase function and decrease pain . However. several fibrocartilage and bone [28] (Figure 1 and Table 1). bone morphogenetic proteins (BMPs) as and repair.11] 30% to 94% . Díaz Heredia J. most of the chanical stress in the regeneration zone . from mechanical improvement of the repair techniques as it corresponds to the bony insertional area. Further basic Zone Histological Collagen type Extracellular matrix and clinical research is needed.i4. reparative and remodelling) used with variable results but stems cell are a more and numerous cells and cytokines have been WJSC|www. Valencia Mora M et al . Rotator cuff disease is bone healing. it also affects athletes and active individuals regardless of age and activity level. and limit the amount of scar tissue.13] bone does not regenerate after repair . This would include growth this specialized tissue does not regenerate after injury factors (GF). Stem cell therapy in the Zone 3 Mineralized II Aggrecan and mineral management of shoulder rotator cuff disorders. The stiffness difference between prognostic factor on function and pain after rotator cuff tendon and bone is responsible for significant me­ repair has been controversial. As to finding ways to improve the biological environment previously mentioned. In an attempt to improve the strength changes that occur in its microstructure. techniques that aim to reproduce the anatomical The enthesis has been divided into four zones: [8.com/1948-0210/full/v7/i4/691. In this direction. [14] properties .691 [23-25] promising alternative . The [3.10. 2015|Volume 7|Issue 4| . it has been demonstrated that [15-22] around that repair . non-mineralized fibrocartilage.wjgnet.v7.2] implications of the ongoing research’s results. Cuéllar R. its histological of the surgical repair.9] footprint of the rotator cuff have been proposed . characteristics composition Zone 1 Tendon I Decorin Zone 2 Non-mineralized II and III Aggrecan and decorin Valencia Mora M. Stem cells have demonstrated great potential in enhancing the biologic healing process based on INTRODUCTION their influence in angiogenesis and the inflammatory [26] The rotator cuff is a structure formed by the tendinous pattern .4252/wjsc. new materials and surgical characteristics and its biomechanical behaviour.htm DOI: http://dx. Barco fibrocartilage ( small amounts of I. as it is well known that area (zone 2). Standard and decorine are also present. Whether or not healing of the tear is a is a complex process. However. the mineralized fibrocartilage. In studies have shown a persistently high failure rate of the tendon area (zone 1) there is a predominance of tendon to bone rotator cuff repair that ranges from type I collagen fibres together with a small amount of [6. type II and III collagen fibres are the delicate and highly specialized fibro-cartilaginous predominant and small amounts of type I. human studies are scarce so the use the four areas of the enthesis [28] of stem cell therapy in rotator cuff repair should still be considered and experimental technique. Zone 4 Bone I Mineral component wjgnet. However.com 692 May 26. The purpose of this paper is to outline the the most common condition of the shoulder for which current knowledge on the role stem cell therapy might patients seek treatment and can be found in 30% to have in dealing with rotator cuff tears and the future 50% of the population aged older than 50 years .4] IN THE ROTATOR CUFF objective of the treatment is the repair of the damaged Tissue regeneration in the tendon-to-bone interphase tendons. decorin which is a small cellular or pericellular matrix The main problem with failure in rotator cuff proteoglycan. The hypo­thesis is that biological the native enthesis is characterized by a predominance therapies might facilitate the regeneration of the of type III collagen due to the excessive formation of normal tendon-to-bone insertion microarchitecture scar tissue and the absence of fibrocartilage. However. mineralized Despite these significant technical advances. org/10. Aggregans [12. several questions still remain before insertions of a group of muscles that dynamically they can be used clinically for augmenting tendon to stabilize the glenohumeral joint. The [27] authors have found that tear recurrence determines enthesis represents a transitional tissue that allows lower functional scores and a decrease in patient for efficient energy transmission due to the gradual [5-7] satisfaction . Ruiz Ibán MA.

where it persisted until 56 d.29. apart The enthesis structure is developed successfully from stem cells. 4 B [13.wjgnet. hematoxilin-eosine. tendon development embryogenic development. Supraspinatus fibroblasts weakness in extracellular matrix. TGF-β1 is active during transcription factors. the formation of could be caused by the incomplete expression of fibrocartilage could be related to a greater expression [28] the genes implicated in its formation . 2015|Volume 7|Issue 4| . development of the physeal plate as (sex determining region Y)-box 9. As the fibers progress into the bone the extracellular matrix is C progresivelyy calcified (zone 3) until it turns into normal bone (zone 4). For example. better in the presence from TGF-β3 to TGF-β1 at 15 d. numerous proteinases are multi-domain proteinases regulated biology-based strategies have been developed in by tissue inhibitors of metalloproteinases (TIMPs) and order to improve the rate and quality of healing in play a determinant role in the remodelling phase. The regeneration of the most specia­ that the stratification in the structure and composition lized zone. Diaz-Heredia et al have studied consequence of the gradual expression of these and the gradual variation of vascular endothelial growth other factors. Ihh and Sox9. 13 and 14 as well as fibroblast growth factor-β (FGF-β BIOLOGIC APPROACH and insulin like growth factor-1 (IGF-1). It has been proposed enthesis zones. On the other hand. healing occurs without would be conditioned by the expression of BMP-12.38] gradual expression of different factors present in the failure in the enthesis . On the member of the basic helix-loop-helix superfamily of contrary. Patched 1. Stem cell therapy for rotator cuff Figure 1 The normal enthesis (longitudinal image 1 and diagram of the bone-tendon junction of the T supraspinatus tendon of a rat. The collagen fiber organization and higher load to ultimate [36. The main areas of research. the mineralized fibrocartilage. during postnatal life. Scleraxis.31] the three phases of the healing process . Para­thyroid GF hormone-related protein (PTHrP) and Indian Heddegog GF factors are key in the development of the different [32-34] (Ihh) has also been studied . inhibition of MMP-13. allows 14 d and it persisted until 56 d. Valencia Mora M et al . biological mechanism of its development could help in pinpointing which factors are relevant in trying to MMP inhibitors [28] regenerate the native transitional tissue . Some authors have pointed transcription factor 2 (Runx2) and bone morphogenetic out that the inability to regenerate the native enthesis protein-2 (BMP2). The GF are WJSC|www. Lastly. rotator cuff models. the amount of mineral factor (VEGF). They are involved in expressed type I collagen during all the process. can be [39] along the different zones of the enthesis could be a stimulated by osteoinductive factors . During of PTHrP. Matrix metallo­ In the past decades. [13. There was a change for higher amount of fibrocartilage formation. In particular. are matrix metalloproteinase (MMP) during embryogenic period so knowledge of the inhibitors and GF. [32] expression of TGF-β1 but with expression of TGF-β3. × 10): the supraspinatus tendon (T) approaches the humeral bone (B) immediately adyacent to the normal carlilage (C). Tissular mineralized fibrocartilage and at 7 d in the mineralized metalloproteinase inhibitors are thus.30] [30] implicated . interleukin-1 (IL-1) and transforming deposit in the mature enthesis could be determined by growth factor-β1 (TGF-β1) in an animal model of the presence of osteogenic factors such as runt-related rotator cuff tears in rats.30. Another important group of factors widely studied are BMP-12. Type X tools. The normal tendon (zone 1) 4 gradually transforms into a fibrocartilaginous tissue with large mononucleated cells (zone 2). tumoral growth. Galatz et MMP expression is increased in degenerative rotator [32] al found that the mature fibrocartilage does not cuff tissue and it is known to cause progressive appear until 21 d after birth. as mentioned before. aneurysmatic disease and post-surgical [35-37] Type II collagen was expressed firstly in the non. tissue remodelling in the rotator cuff . Scleraxis is a protein which determines an absence of scar tissue. a MMP that collagen was initially seen in mineralized collagen at is increased in degenerative rotator cuff tears. potential biological fibrocartilage. tenomoduline and scleraxis .com 693 May 26. Further explanation of the biochemical 3 environment of these zones is shown in Table 1.

Gulotta et al have used gene­ management of tendinopathies and management of tically modified MSCs in order to express scleraxis and [54-56] muscle lesions . of the rotator cuff has been autologous bone marrow other investigators support the use of PRP in selected [20] (BM-MSCs). there is increasing knowledge that certain MSC Despite the variable results obtained. Randelli et al in a prospective unilateral detachment of supraspinatus tendon and a randomized clinical trial. Applications in which its usefulness has been drilling and the subsequent migration of stem cells confirmed are: treatment of bone defects. is platelet tissue sources have been identified: bone marrow. TGFβ2. fat. origins have been used for rotator cuff repair. MD). BM-MSCs were harvested and accelerated healing rate in patients with non. MSCs of different their effects. Results [57] for the use of allogenic strains . MSCs of into the suture zone. Valencia Mora M et al . demonstrated improved biomechanical strength at 4 wk [63] Furthermore. They showed that MSCs chronic nature of these injuries. fibrocartilage fibers. Although they did not find [53] enhance its benefits . Gulotta et al performed an experimental [52] [25] cases . with their innate ability to differentiate expressed green fluorescent protein in the bone into several mesenchymal tissues including bone. Although generally speaking MSCs promotes glucosamine synthesis and serves as a of different origins have similar biological potential. however. Kida [62] et al designed a study in which they performed STEM CELL THERAPY: ANIMAL STUDIES additional drilling to the greater tuberosity to release The use of stem cell therapy in the regeneration of bone marrow and allow bone marrow cells to migrate musculoskeletal tissue is a very dynamic field. Another explanation for this fact significant differences in between the treated and is that the expression of growth factors is ephemeral. Bone marrow MSCs [24] [51] Neither Sánchez Márquez et al or Ruiz-Moneo et al found any relevant clinical improvement with the use The principal source for stem cell-enhanced healing of PRP to augment suture in massive tears.44] [45] [15] BMP-14 .41] sutures. With regards to its application in rotator investigations performed on rotator cuff repair. More recently. meniscal regeneration and healing. there was a higher amount In this context. load to failure. MSCs over embryonic of fetal stem cells as the former MSCs genetically modified to over-express MT1- are usually locally available and easier to obtain for MMP might be useful for augmenting suture as it has the treatment of these non-life-threatening problems.com 694 May 26. found less postoperative pain transosseous repair in rats. Rodeo et grafts in a bone tunnel. In this animal model.40. periosteum. equilibrates angiogenesis. pluripotent cell . tendinous or cartilaginous regeneration . both femoral and tibiae bones and pull out strength is [58] TGF-β3 and FGF. the low immunogenicity of MSCs allows based on a higher presence of fibrocartilage . cartilage might improve maximum load to failure at 4 and 8 wk. adipose tissue. fibrin gels or collagen sponges . cuff tears. research in animal bone-to-tendon healing models. [46] rich plasma (PRP) obtained from autologous blood . For example. However. Investigators usually prefer adult produce MIT1 and BMP-13 with promising results. of studies with application of MSCs genetically modified [64] Some authors have also performed extensive to overexpress BMP-13 were not that successful. Table 2 shows the main animal [47-50] injuries . [43] [40. tendon. BMP-13 . it has been used populations are better than others for specific tissue [59-61] for muscular. TGFβ1. In order to reproduce rotator cuff surgery. the results have also been controversial. They tested chimeric rats that different origins. muscle.wjgnet. untreated groups. by performing lavage of intramedullary canals of massive rotator cuff tears but there were no differences long bones with Hank’s Balanced Salt Solution in functional scores and re-rupture rate. Due to the (Gibco. stem cell and gene therapies could be a of fibrocartilage formation and better orientation of more definitive and long-lasting treatment. have and homeostasis. Other investigators have rabbits and found a significant increase in maximum [42] [17] obtained similar results with BMP-12 . at 4 wk. 4 and 8 wk. [23] cellular support for migration and differentiation . restores all been evaluated as sources of multipotent and [26] intraarticular hyaluronic acid. FGF . They detected better histologic and tested. stimulates wound closure. MSCs genetically modified with Until recently the most widespread model reproduced Scx demonstrated to promote better biomechanical WJSC|www. It seems that repair. On the contrary. Different The most widespread treatment. it has been suggested were present at the repair site and that they were that PRP application should be serial in order to metabolically active. Some of It was not until 2009 that MSC therapy was applied these factors seem to play different roles depending to a rotator cuff model. 2015|Volume 7|Issue 4| . since then the available in which zone of the enthesis they act or the timing of literature has grown consistently. synovia. It has been proposed that PRP facilitates coagulation dermis and umbilical cord or peripheral blood. such as augmented the integration of anterior cruciate ligament tendinous [16. marrow cells and looked for the expression of this muscle and tendon have been used extensively in tissue protein after a period of 2. Lim et al have used MSCs in this model in [16] biomechanical properties . the [16] al developed an animal model of supraspinatus repair hams­tring grafts are introduced into bony tunnels in in sheep in which they used BMP-2 to 7. [63-65] regeneration. Stem cell therapy for rotator cuff usually delivered with a vehicle. IGF-1 and PDGF-b . ligamentous. Gaithersburg.

BMP-13: Bone morphogenetic protein-13. [69] myogenic cells . They found better healing properties and of the cells and avoid contact in between them. promote a capacity of regeneration after fatty infiltration of the the chondrogenic differentiation and avoid expression muscle. Tendon derived MSCs (T-MSCs) or Adipose derived MSCs (A-MSCs). saline and AMSCs. Numerous different scaffolds as polyglicolic acid. The authors suggest that more started developing different strategies for the clinical studies are necessary before assuming that M-MSCs application of the experimental findings. Due to its meso­ Cell adhesion to the scaffold depends on the interaction dermal origin. they can differentiate into adipose lineage that is established in between the scaffold microstructure [67] [68] [59] cells . supporting the previous experimental [62] samples. Beitzel et al studied the quantity and chara­ [74] Lastly. response but increased fibroblastic cell ingrowth and reduced infiltration of lymphocytes. Rotator cuff derived MSCs rabbit rotator cuff defect did not elicit an immunologic have been isolated and compared to BM-derived stem WJSC|www. they have also demonstrated Transmembrane contacts are key factor for MSC sur­ [75] their capacity to differentiate into adipose tissue using vival.com 695 May 26. some authors have resident tendon fibers. of type I collagen. Pelinkovic et al [73] have shown that the STEM CELL THERAPY: HUMAN STUDIES injection of M-MSCs into the supraspinatus tendon of Although there is a lack of consensus on whether athymic rats resulted in the engraftment of transplanted the application of stem cells to enhance the rotator cells in a pattern with a morphology comparable to cuff healing is effective or not. Acute repair Improved biomechanical strength MMP Gulotta et al[64] Rat Allogenic BM-MSCs Supraspinatus tendon Fibrin glue carrier No differences in structure. Shen et al performed a study using cteristics of BM-MSCs obtained from proximal humerus tenocyte-derived stem cells (T-MSCs) proliferated in and distal femur bone marrow aspiration and found vitro and obtained from human fetal Achilles tendon them comparable. in different scaffolds and have demonstrated that the [71] Recently.wjgnet. Vehicles that maintain the rounded shape only suture. Stem cell therapy for rotator cuff Table 2 Rotator cuff repair animal models using mesenchimal stem cells Ref. Porous gelatine vehicles or those that use fibrin favour a fibro cartilaginous phenotype due to MSCs of other origins (non-hematopoyetic) [76] the expression of collagen types I and II . Oh et al have published the first study scaffold can determine the differentiation capacity [75] in a rotator cuff model using AMSCs. In vivo. Adipose tissue MSC Adipose Tissue derived stem cells (AMSC) have also Choice of scaffold for MSCs deployment [66] shown multipotentiality in vitro . Two different types compared for a suture of the subscapularis tendon in of interactions have been described: physical and rabbit using saline. composition or strength Acute repair at the repair site Gulotta et al[63] Rat Allogenic BM-MSCs Supraspinatus tendon Fibrin glue carrier Improved fibrocartilage transduced with MT1. Muscle-derived stem cells (M-MSCs) have been isolated using a modification of a method known as the preplate [72] technique . collagen sponges studies have investigated the behaviour of stem cells [54. composition or strength transduced with human Acute repair at the repair site BMP-13 Gulotta et al[65] Rat Allogenic BM-MSCs Supraspinatus tendon Fibrin glue carrier Improved fibrocartilage transduced with sleraxis Acute repair Improved mechanical resistance and stiffness Shen et al[74] Rabbit Allogenic T-MSCs Supraspinatus tendon Seeded scaffold T-MSCs differentiated into tenocytes Acute repair (silk-collagen) Improved collagen content Improved biological environment Less inflammation Kida et al[62] Rat Autologous BM-MSC Supraspinatus tendon Transosseous BM-MSCs infiltrated the repaired tendon Acute repair drilling Improved mechanical resistance Oh et al[71] Rabbit Allogenic A-MSCs Subscapularis tendon Injection Improved muscle function Chronic repair Improved tendon healing Decreased fatty infiltration Different types of cells have been used: Bone marrow derived MSCs (BM-MSCs). Four groups were into one or other lineages . osteogenic cells . chondrogenic cells and and the cell surface receptors denominated integrins. only AMSCs and biochemical. MSCs: Mesenchymal stem cells. [65] characteristics at 2 wk . 2015|Volume 7|Issue 4| .71] or fibrin gel . Animal Type of cells Tendon repair model Method of Results delivery Gulotta et al[20] Rat Allogenic BM-MSC Supraspinatus tendon Fibrin glue carrier No differences in structure.70. [77] can improve rotator cuff healing. Valencia Mora M et al . Implantation of this type of cells in the research by Kida et al . MT1- MMP: Metalloproteinase inhibitor-1. proliferation and differentiation .

Galatz LM. Middleton WD. Part I: Footprint contact characteristics for a transosseous- men­tation. [81] and magnetic resonance imaging results . This could be useful in order to avoid [80] of biceps tendon.1016/j.1177/0363546509359679] cells. J Shoulder Elbow Surg 2007. Caldwell JM.2106/JBJS. Bisson LJ. A molecular morphology were evaluated by histologic analysis perspective.017] 4 Harryman DT. However. Tibone JE. Generation of iPS Cuff integrity after arthroscopic versus open rotator cuff repair: a cells can use viral or. A better knowledge of the 5 Yoo JH. Jun BJ. Flatow EL. Factors affecting outcome after structural tissue healing may provide a great potential for func­ failure of repaired rotator cuff tears.com 696 May 26. Factors affecting healing comes to oncologic and teratogenic risks .wjgnet. 23942286 DOI: 10. Lee On the other hand. Rhee YG. transgenic therapies lack safety clearance when it [26] Steger-May K. Valencia Mora M et al . Levine WN. practice. CONCLUSION [81] Ellera Gomes et al published their work in 14 Current literature regarding the clinical use of stem patients with a complete tear of the rotator cuff that cells in rotator cuff tears is limited. Moreover. Hollins AM. J Bone Joint or modifications to the culture conditions to generate Surg Am 2014. nonviral vector prospective study. these 16679227 DOI: 10. Buza JA.017] 11 Tashjian RZ. Although in vivo was repaired in a trans osseous fashion through a animal studies have shown promising results to enhance mini-incision augmenting the suture with mononuclear tendon-to-bone healing. It seems that the myogenic potential of MSCs into complex. Klepps S. The pathogenesis of tendinopathy. specific growth factor supple­ TQ. Lo IK. J Bone Joint Surg Am 2003.1016/j. to use biodegradable polymer scaffolds to promote [78] [79] MSCs . 12 of the 14 tears had healed according to clinical technique. as well as on histologic of rotator cuff disease. 38: 2435-2442 [PMID: 21030564 DOI: 10. viable 3D tissues. Stem cell therapy for rotator cuff cells.28] identify the growth factors and proteins to target . Chamberlain AM. Cho NS. Am J Sports Lastly. rates after arthroscopic double-row rotator cuff repair. Hildebolt CF.1177/0363546513499152] A combination of stem cells. 2015|Volume 7|Issue 4| . ElAttrache NS. Ditsios K. Galatz LM. Hettrich CM. Katz JN. a desired phenotype is one of the most investigated L. in the form of transgenic therapy may equivalent rotator cuff repair technique compared with a double- allow longer-term tendon repair and potential return row repair technique. Utsunomiya et al also studied the scarring during the healing process. Warner JJ. A prospective multipractice investigation of FUTURE ALTERNATIVES patients with full-thickness rotator cuff tears: the importance of Advanced stem cell therapy and gene therapy repre­ comorbidities. [PMID: 16882890 DOI: 10. Keener JD. 12867575 DOI: 10.00551] tional restoration . Buyea C. the newly recognized anti. 8 Park MC. Millett PJ.1016/j. Fetal-derived embryonic stem cell-like cells [PMID: 17321161 DOI: 10. Further basic and clinical research is needed. inflammatory and antiapoptotic impact of MSCs on Yamaguchi K.2006. According to their findings.010] have recently been evaluated for tendon and ligament 9 Duquin TR. Donegan RP. Which method of rotator cuff repair leads to the highest rate of structural healing? A systematic repair. Am J Sports Med 2013.1002/art.2010. subacromial bursa as a potential source for MSCs and found that the synovial cells found in the bursa were a good cell source. Ahmad CS. 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mononuclear autologous stem cells. Huang TF.2012. Am J Sports Med 2013. Guilak F. 29: 301-308 [PMID: 23290182 DOI: 10. Conventional rotator cuff repair complemented by the aid of F. Knee Surg Sports Traumatol Anastasia L. Tettamanti G. Sekiya I. Gagliano N. 5: 6512473572] 362-369 [PMID: 14578098 DOI: 10.1007/ cuff and long head of biceps tendon cells possessing stem cell-like s00167-011-1607-9] self-renewal and multipotential differentiation capacity. Ragone V.Editor: Wu HL WJSC|www. Valencia Mora M et al . Cytotherapy 2003. Chiang ER. Liu L. Med 2013. Pixley J S.Editor: Ji FF L. Isolation of stem cells derived from shoulder tissues involved in rotator cuff mesenchymal stem cells from shoulder rotator cuff: a potential tears. and differentiation potential. 41: 657-668 [PMID: 23371475 DOI: source for muscle and tendon repair. Adipose-derived adult stem cells: isolation. da Silva RC.1016/ 80 Utsunomiya H. Cirillo R. Hung SC. Pellanda 79 Randelli P. Uchida S. Tringali C. Isolation and characterization of human mesenchymal 78 Tsai CC.3727/096368912X656090] 81 Ellera Gomes JL. Cell Transplant 2013. Silla LM. Abreu MR. Isolation and characterization of 2 new human rotator Arthrosc 2012.1177/0363546512473269] 413-422 [PMID: 23006509 DOI: 10.com 699 May 26.arthro. Conforti E. j. Stem cell therapy for rotator cuff Arthroscopy 2013. Masuzzo P.021] Nakamura T. Ma HL. Li SC. Am J Sports 82 Gimble J.1080/14653240310003026] P.wjgnet.1177/036354 characterization.08. Moridera K.Reviewer: Hanypsiak BT. Piccoli M. Sakai A. 41: 1653-1664 [PMID: 23393078 DOI: 10. Cabitza P.Editor: A E. 20: 373-377 [PMID: 21773831 DOI: 10. 22: 10. Creo P. 2015|Volume 7|Issue 4| .

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