Assessment of stem cell carriers for tendon tissue engineering in pre-clinical models

Tendon injuries are prevalent and problematic, especially among young and otherwise healthy individuals. The inherently slow innate healing process combined with the inevitable scar tissue formation compromise functional recovery, imposing the need for the development of therapeutic strategies. The limited number of low activity/reparative capacity tendon-resident cells has directed substantial research efforts towards the exploration of the therapeutic potential of various stem cells in tendon injuries and pathophysiologies. Severe injuries require the use of a stem cell carrier to enable cell localisation at the defect site. The present study describes advancements that injectable carriers, tissue grafts, anisotropically orientated biomaterials, and cell-sheets have achieved in preclinical models as stem cell carriers for tendon repair.

[1]  Dimitrios I. Zeugolis,et al.  Tendons: Engineering of Functional Tissues , 2011 .

[2]  Jiake Xu,et al.  Scaffolds for tendon and ligament repair: review of the efficacy of commercial products , 2009, Expert review of medical devices.

[3]  Dimitrios I. Zeugolis,et al.  Nano-textured self-assembled aligned collagen hydrogels promote directional neurite guidance and overcome inhibition by myelin associated glycoprotein , 2011 .

[4]  F. Watt,et al.  The therapeutic potential of stem cells , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[5]  Dave Balachandran,et al.  Incorporation of a decorin biomimetic enhances the mechanical properties of electrochemically aligned collagen threads. , 2011, Acta biomaterialia.

[6]  C T Laurencin,et al.  Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems , 2011, Biomedical materials.

[7]  S. Nakamura,et al.  Tendon Grafting for Multiple Extensor Tendon Ruptures of Fingers in Rheumatoid Hands , 2002, Journal of hand surgery.

[8]  P. Clegg,et al.  Stem cells in veterinary medicine--attempts at regenerating equine tendon after injury. , 2007, Trends in biotechnology.

[9]  Guangdong Zhou,et al.  In vivo engineering of a functional tendon sheath in a hen model. , 2010, Biomaterials.

[10]  H. Ouyang,et al.  Stem cells for tendon tissue engineering and regeneration , 2010, Expert opinion on biological therapy.

[11]  Jean C. Y. Wang Evaluating therapeutic efficacy against cancer stem cells: new challenges posed by a new paradigm. , 2007, Cell stem cell.

[12]  Natalia Juncosa-Melvin,et al.  The use of mesenchymal stem cells in collagen-based scaffolds for tissue-engineered repair of tendons , 2010, Nature Protocols.

[13]  Christian Krettek,et al.  Tissue engineering of tendons and ligaments by human bone marrow stromal cells in a liquid fibrin matrix in immunodeficient rats: Results of a histologic study , 2007, Archives of Orthopaedic and Trauma Surgery.

[14]  Techung Lee Stem cell therapy independent of stemness. , 2012, World journal of stem cells.

[15]  Zi Yin,et al.  The regulation of tendon stem cell differentiation by the alignment of nanofibers. , 2010, Biomaterials.

[16]  Abhay Pandit,et al.  Preferential tendon stem cell response to growth factor supplementation , 2016, Journal of tissue engineering and regenerative medicine.

[17]  Albert J. Keung,et al.  Presentation counts: microenvironmental regulation of stem cells by biophysical and material cues. , 2010, Annual review of cell and developmental biology.

[18]  K. Kraus,et al.  Collagen fabrics as biomaterials , 1994, Biotechnology and bioengineering.

[19]  Natalia Juncosa-Melvin,et al.  Effects of cell-to-collagen ratio in stem cell-seeded constructs for Achilles tendon repair. , 2006, Tissue engineering.

[20]  J. Macdermid,et al.  Effects of low power laser irradiation on bone healing in animals: a meta-analysis , 2010, Journal of orthopaedic surgery and research.

[21]  Young-Jin Ju,et al.  Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing , 2008, Cell and Tissue Research.

[22]  Freddie H. Fu,et al.  Isolation and characterization of human anterior cruciate ligament-derived vascular stem cells. , 2012, Stem cells and development.

[23]  D. Zeugolis,et al.  Engineering in vitro microenvironments for cell based therapies and drug discovery. , 2013, Drug discovery today.

[24]  M. Raghunath,et al.  Collagen: Materials Analysis and Implant Uses , 2011 .

[25]  Tung-Fu Huang,et al.  Mesenchymal Stem Cells From a Hypoxic Culture Improve and Engraft Achilles Tendon Repair , 2013, The American journal of sports medicine.

[26]  G. Murrell,et al.  The Basic Science of Tendinopathy , 2008, Clinical orthopaedics and related research.

[27]  J. Hong,et al.  Single-stage Achilles tendon reconstruction using a composite sensate free flap of dorsalis pedis and tendon strips of the extensor digitorum longus in a complex wound. , 2003, Annals of plastic surgery.

[28]  Freddie H. Fu,et al.  Tendon graft revitalization using adult anterior cruciate ligament (ACL)-derived CD34+ cell sheets for ACL reconstruction. , 2013, Biomaterials.

[29]  M. Järvinen,et al.  Collagen fibres of the spontaneously ruptured human tendons display decreased thickness and crimp angle , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  Sambit Sahoo,et al.  Bioactive nanofibers for fibroblastic differentiation of mesenchymal precursor cells for ligament/tendon tissue engineering applications. , 2010, Differentiation; research in biological diversity.

[31]  W. Lu,et al.  Extracellular Matrix Stability of Primary Mammalian Chondrocytes and Intervertebral Disc Cells Cultured in Alginate-Based Microbead Hydrogels , 2008, Cell transplantation.

[32]  H. Bannasch,et al.  Skin tissue engineering. , 2003, Clinics in plastic surgery.

[33]  Margaret Clotworthy,et al.  On the effects of cycloheximide on cell motility and polarisation in Dictyostelium discoideum , 2006, BMC Cell Biology.

[34]  Gil Navon,et al.  Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. , 2006, The Journal of clinical investigation.

[35]  D L Butler,et al.  Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[36]  James Chang,et al.  A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. , 2007, The Journal of hand surgery.

[37]  S. Ikehara,et al.  Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy. , 2010, The Journal of bone and joint surgery. American volume.

[38]  H. Harn,et al.  Stem Cell Therapy for Tendon Injury , 2013, Cell transplantation.

[39]  W. Friess,et al.  Collagen--biomaterial for drug delivery. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[40]  Hongbin Fan,et al.  Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model. , 2009, Biomaterials.

[41]  Y. Oka Reconstruction of the flexor pollicis longus tendon ruptured, but untreated, during infancy. , 2000, The Tokai journal of experimental and clinical medicine.

[42]  Masayuki Yamato,et al.  Tissue Engineering Based on Cell Sheet Technology , 2007 .

[43]  Po-Jung Chu,et al.  Extensor-tendons reconstruction using autogenous palmaris longus tendon grafting for rheumatoid arthritis patients , 2008, Journal of orthopaedic surgery and research.

[44]  P. Kannus Structure of the tendon connective tissue , 2000, Scandinavian journal of medicine & science in sports.

[45]  Umut A. Gurkan,et al.  An electrochemical fabrication process for the assembly of anisotropically oriented collagen bundles. , 2008, Biomaterials.

[46]  Jess G. Snedeker,et al.  Paracrine Interactions between Mesenchymal Stem Cells Affect Substrate Driven Differentiation toward Tendon and Bone Phenotypes , 2012, PloS one.

[47]  D. Butler,et al.  Repair of patellar tendon injuries using a cell–collagen composite , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[48]  Mitsuo Ochi,et al.  Rotator Cuff Regeneration Using a Bioabsorbable Material With Bone Marrow–Derived Mesenchymal Stem Cells in a Rabbit Model , 2012, The American journal of sports medicine.

[49]  J. Itskovitz‐Eldor,et al.  Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues. , 2010, Tissue engineering. Part A.

[50]  Wei Xu,et al.  Human iPSC-derived neural crest stem cells promote tendon repair in a rat patellar tendon window defect model. , 2013, Tissue engineering. Part A.

[51]  J. Karp,et al.  Prodrugs as self-assembled hydrogels: a new paradigm for biomaterials. , 2013, Current opinion in biotechnology.

[52]  D. Zeugolis,et al.  2.222 – Xenogenic Tissues and Biomaterials for the Skeletal System , 2011 .

[53]  Hiko Hyakusoku,et al.  Adipose-derived stem cells enhance primary tendon repair: biomechanical and immunohistochemical evaluation. , 2012, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[54]  M. R. Jackson,et al.  Fibrin sealants in surgical practice: An overview. , 2001, American journal of surgery.

[55]  Yan Wang,et al.  Engineered scaffold-free tendon tissue produced by tendon-derived stem cells. , 2013, Biomaterials.

[56]  Bing Xu,et al.  D-glucosamine-based supramolecular hydrogels to improve wound healing. , 2007, Chemical communications.

[57]  S. Bergante,et al.  Isolation and Characterization of 2 New Human Rotator Cuff and Long Head of Biceps Tendon Cells Possessing Stem Cell–Like Self-Renewal and Multipotential Differentiation Capacity , 2013, The American journal of sports medicine.

[58]  Shi-wu Dong,et al.  Synergy of tendon stem cells and platelet‐rich plasma in tendon healing , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[59]  H. Ouyang,et al.  The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair. , 2013, Acta biomaterialia.

[60]  Rocky S Tuan,et al.  Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix. , 2013, Biomaterials.

[61]  A. Möller,et al.  Increasing incidence of Achilles tendon rupture. , 1996, Acta orthopaedica Scandinavica.

[62]  Zi Yin,et al.  Stepwise Differentiation of Human Embryonic Stem Cells Promotes Tendon Regeneration by Secreting Fetal Tendon Matrix and Differentiation Factors , 2009, Stem cells.

[63]  F. Cellesi Thermoresponsive hydrogels for cellular delivery. , 2012, Therapeutic delivery.

[64]  RICHARD A.F. CLARK,et al.  Fibrin and Wound Healing , 2001 .

[65]  A. Goodship,et al.  Isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment. , 2010, Equine veterinary journal.

[66]  Jason Wong,et al.  Types and epidemiology of tendinopathy. , 2003, Clinics in sports medicine.

[67]  V. Thomas,et al.  The treatment of ruptures of multiple extensor tendons at wrist level by a free tendon graft in the rheumatoid patient. , 1987, The Journal of hand surgery.

[68]  N. Maffulli,et al.  Tendon repair through stem cell intervention: Cellular and molecular approaches , 2008, Disability and rehabilitation.

[69]  P. Lui,et al.  Cell therapy for the treatment of tendinopathy--a systematic review on the pre-clinical and clinical evidence. , 2013, Seminars in arthritis and rheumatism.

[70]  K. Kashiwagi,et al.  Effects of transforming growth factor-β 1 on the early stages of healing of the Achilles tendon in a rat model , 2004 .

[71]  A. Tria,et al.  Regeneration of Achilles tendon with a collagen tendon prosthesis. Results of a one-year implantation study. , 1991, The Journal of bone and joint surgery. American volume.

[72]  Fabio Carlucci,et al.  Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses. , 2007, Tissue engineering.

[73]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[74]  G. Pins,et al.  Characterizing fibroblast migration on discrete collagen threads for applications in tissue regeneration. , 2004, Journal of biomedical materials research. Part A.

[75]  M B McCarthy,et al.  RGD-tethered Silk Substrate Stimulates the Differentiation of Human Tendon Cells , 2006, Clinical orthopaedics and related research.

[76]  D. Covas,et al.  Mechanisms involved in the therapeutic properties of mesenchymal stem cells. , 2009, Cytokine & growth factor reviews.

[77]  R. Gelberman,et al.  The alchemy of tendon repair: a primer for the (S)mad scientist. , 2006, The Journal of clinical investigation.

[78]  Alan W. Flake,et al.  Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep , 2000, Nature Medicine.

[79]  Beng Hai Lim,et al.  Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. , 2007, The Journal of bone and joint surgery. American volume.

[80]  N. Maffulli,et al.  Biology of tendon injury: healing, modeling and remodeling. , 2006, Journal of musculoskeletal & neuronal interactions.

[81]  B. Hazleman,et al.  Endochondral ossification in Achilles and patella tendinopathy. , 2002, Rheumatology.

[82]  Ralph Weissleder,et al.  Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy , 2009, Proceedings of the National Academy of Sciences.

[83]  D. Link,et al.  Hypoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells , 2008, Stem cells.

[84]  J. Tanaka,et al.  Biomimetic configurational arrays of hydroxyapatite nanocrystals on bio-organics. , 2001, Biomaterials.

[85]  Brian A. Aguado,et al.  Improving viability of stem cells during syringe needle flow through the design of hydrogel cell carriers. , 2012, Tissue engineering. Part A.

[86]  L. Fortier,et al.  Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. , 2012, The Journal of bone and joint surgery. American volume.

[87]  S. Teoh,et al.  Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon. , 2003, Tissue engineering.

[88]  Fulin Chen,et al.  Platelet-rich plasma - A promising cell carrier for micro-invasive articular cartilage repair. , 2009, Medical hypotheses.

[89]  Rocky S Tuan,et al.  Novel strategies in tendon and ligament tissue engineering: Advanced biomaterials and regeneration motifs , 2010, Sports medicine, arthroscopy, rehabilitation, therapy & technology : SMARTT.

[90]  Marian F Young,et al.  Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche , 2007, Nature Medicine.

[91]  W. Keith,et al.  Therapeutic potential of adult stem cells. , 2006, European journal of cancer.

[92]  Neil Rushton,et al.  Collagen fibre implant for tendon and ligament biological augmentation. In vivo study in an ovine model , 2013, Knee Surgery, Sports Traumatology, Arthroscopy.

[93]  P. Lui,et al.  Does erroneous differentiation of tendon-derived stem cells contribute to the pathogenesis of calcifying tendinopathy? , 2011, Chinese medical journal.

[94]  J. Wang,et al.  Tendinopathy and its treatment with platelet-rich plasma (PRP). , 2013, Histology and histopathology.

[95]  J. Wang,et al.  The role of engineered tendon matrix in the stemness of tendon stem cells in vitro and the promotion of tendon-like tissue formation in vivo. , 2011, Biomaterials.

[96]  W. Walsh,et al.  Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes , 2013, Archives of Orthopaedic and Trauma Surgery.

[97]  Roger K. Smith Mesenchymal stem cell therapy for equine tendinopathy , 2008, Disability and rehabilitation.

[98]  G. Daley,et al.  Therapeutic potential of embryonic stem cells. , 2005, Blood reviews.

[99]  J. Goh,et al.  The effect of fibrin glue on tendon healing and adhesion formation in a rabbit model of flexor tendon injury and repair , 2013, Journal of plastic surgery and hand surgery.

[100]  J. Goh,et al.  An Analysis of Soft Tissue Allograft Anterior Cruciate Ligament Reconstruction in a Rabbit Model , 2007, The American journal of sports medicine.

[101]  C. Vaquette,et al.  Aligned poly(L-lactic-co-e-caprolactone) electrospun microfibers and knitted structure: a novel composite scaffold for ligament tissue engineering. , 2010, Journal of biomedical materials research. Part A.

[102]  Ralph Müller,et al.  Smad8/BMP2‐engineered mesenchymal stem cells induce accelerated recovery of the biomechanical properties of the achilles tendon , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[103]  Jason A. Burdick,et al.  Hyaluronic Acid Hydrogels for Biomedical Applications , 2011, Advanced materials.

[104]  R. Arciero,et al.  The Positive Effects of Different Platelet-Rich Plasma Methods on Human Muscle, Bone, and Tendon Cells , 2012, The American journal of sports medicine.

[105]  Vasili Karas,et al.  Platelet-rich plasma: a milieu of bioactive factors. , 2012, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[106]  D. Zeugolis,et al.  Preferential cell response to anisotropic electro-spun fibrous scaffolds under tension-free conditions , 2011, Journal of Materials Science: Materials in Medicine.

[107]  J. Dudhia,et al.  Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. , 2012, Equine veterinary journal.

[108]  M. Hincke,et al.  Fibrin: a versatile scaffold for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[109]  Ali Khademhosseini,et al.  Bioinspired materials for controlling stem cell fate. , 2010, Accounts of chemical research.

[110]  D L Butler,et al.  Autologous mesenchymal stem cell-mediated repair of tendon. , 1999, Tissue engineering.

[111]  D. Butler,et al.  Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[112]  Pierre Weiss,et al.  An injectable vehicle for nucleus pulposus cell-based therapy. , 2011, Biomaterials.

[113]  Christian Krettek,et al.  Bone marrow stromal cells in a liquid fibrin matrix improve the healing process of patellar tendon window defects. , 2009, Tissue engineering. Part A.

[114]  L. Qin,et al.  Biology and augmentation of tendon-bone insertion repair , 2010, Journal of orthopaedic surgery and research.

[115]  David Butler,et al.  What we should know before using tissue engineering techniques to repair injured tendons: a developmental biology perspective. , 2011, Tissue engineering. Part B, Reviews.

[116]  R. Cameron,et al.  Regeneration and repair of tendon and ligament tissue using collagen fibre biomaterials. , 2011, Acta biomaterialia.

[117]  M. Marcacci,et al.  Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use , 2011, Knee Surgery, Sports Traumatology, Arthroscopy.

[118]  V. Wright,et al.  Application of Platelet-Rich Plasma to Enhance Tissue Repair , 2010 .

[119]  D. Docheva,et al.  Comparison of tenocytes and mesenchymal stem cells seeded on biodegradable scaffolds in a full-size tendon defect model , 2012, Journal of Materials Science: Materials in Medicine.

[120]  T. O’Brien,et al.  A comparison of the efficacy of transplantation of bone marrow-derived mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute myocardial infarction , 2012, Stem Cell Research & Therapy.

[121]  Matthias P. Lutolf,et al.  Designing materials to direct stem-cell fate , 2009, Nature.

[122]  P. McArthur,et al.  Free Tendon Interposition Grafting for the Repair of Ruptured Extensor Tendons in the Rheumatoid Hand , 1998, Journal of hand surgery.

[123]  S. Kostin,et al.  Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. , 2008, Cell stem cell.

[124]  D. Butler,et al.  Tendon tissue engineering: progress, challenges, and translation to the clinic. , 2011, Journal of musculoskeletal & neuronal interactions.

[125]  G. Boivin,et al.  Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[126]  F. Munarin,et al.  New Perspectives in Cell Delivery Systems for Tissue Regeneration: Natural-derived Injectable Hydrogels , 2012, Journal of applied biomaterials & functional materials.

[127]  C. Bearzi,et al.  Tissue engineering for skeletal muscle regeneration. , 2012, Muscles, ligaments and tendons journal.

[128]  G. Murrell,et al.  The Roles of Growth Factors in Tendon and Ligament Healing , 2003, Sports medicine.

[129]  J. Feijen,et al.  Mechanical properties of single electrospun collagen type I fibers. , 2008, Biomaterials.

[130]  R. Gelberman,et al.  Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair. , 2013, Acta biomaterialia.

[131]  Freddie H. Fu,et al.  Therapeutic Potential of Anterior Cruciate Ligament-Derived Stem Cells for Anterior Cruciate Ligament Reconstruction , 2012, Cell transplantation.

[132]  I. Marcoccio,et al.  Flap coverage of dorsum of hand associated with extensor tendons injuries: A completely vascularized single‐stage reconstruction , 2003, Microsurgery.

[133]  M. Raghunath,et al.  Electro-spinning of pure collagen nano-fibres - just an expensive way to make gelatin? , 2008, Biomaterials.