Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. 2007

Alphonsus K S Chong, and Abel D Ang, and James C H Goh, and James H P Hui, and Aymeric Y T Lim, and Eng Hin Lee, and Beng Hai Lim
Department of Hand and Reconstructive Microsurgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. alfchong@gmail.com

BACKGROUND A repaired tendon needs to be protected for weeks until it has accrued enough strength to handle physiological loads. Tissue-engineering techniques have shown promise in the treatment of tendon and ligament defects. The present study tested the hypothesis that bone marrow-derived mesenchymal stem cells can accelerate tendon-healing after primary repair of a tendon injury in a rabbit model. METHODS Fifty-seven New Zealand White rabbits were used as the experimental animals, and seven others were used as the source of bone marrow-derived mesenchymal stem cells. The injury model was a sharp complete transection through the midsubstance of the Achilles tendon. The transected tendon was immediately repaired with use of a modified Kessler suture and a running epitendinous suture. Both limbs were used, and each side was randomized to receive either bone marrow-derived mesenchymal stem cells in a fibrin carrier or fibrin carrier alone (control). Postoperatively, the rabbits were not immobilized. Specimens were harvested at one, three, six, and twelve weeks for analysis, which included evaluation of gross morphology (sixty-two specimens), cell tracing (twelve specimens), histological assessment (forty specimens), immunohistochemistry studies (thirty specimens), morphometric analysis (forty specimens), and mechanical testing (sixty-two specimens). RESULTS There were no differences between the two groups with regard to the gross morphology of the tendons. The fibrin had degraded by three weeks. Cell tracing showed that labeled bone marrow-derived mesenchymal stem cells remained viable and present in the intratendinous region for at least six weeks, becoming more diffuse at later time-periods. At three weeks, collagen fibers appeared more organized and there were better morphometric nuclear parameters in the treatment group (p < 0.05). At six and twelve weeks, there were no differences between the groups with regard to morphometric nuclear parameters. Biomechanical testing showed improved modulus in the treatment group as compared with the control group at three weeks (p < 0.05) but not at subsequent time-periods. CONCLUSIONS Intratendinous cell therapy with bone marrow-derived mesenchymal stem cells following primary tendon repair can improve histological and biomechanical parameters in the early stages of tendon-healing.

UI MeSH Term Description Entries
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D000125 Achilles Tendon Tendon that connects the muscles in the back of the calf to the HEEL BONE. Calcaneal Tendon,Tendo Calcaneus,Calcaneal Tendons,Tendon, Achilles,Tendon, Calcaneal,Tendons, Calcaneal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013536 Suture Techniques Techniques for securing together the edges of a wound, with loops of thread or similar materials (SUTURES). Suture Technics,Suture Technic,Suture Technique,Technic, Suture,Technics, Suture,Technique, Suture,Techniques, Suture
D013708 Tendon Injuries Injuries to the fibrous cords of connective tissue which attach muscles to bones or other structures. Injuries, Tendon,Injury, Tendon,Tendon Injury
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D015718 Fibrin Tissue Adhesive An autologous or commercial tissue adhesive containing FIBRINOGEN and THROMBIN. The commercial product is a two component system from human plasma that contains more than fibrinogen and thrombin. The first component contains highly concentrated fibrinogen, FACTOR VIII, fibronectin, and traces of other plasma proteins. The second component contains thrombin, calcium chloride, and antifibrinolytic agents such as APROTININ. Mixing of the two components promotes BLOOD CLOTTING and the formation and cross-linking of fibrin. The tissue adhesive is used for tissue sealing, HEMOSTASIS, and WOUND HEALING. Autologous Fibrin Tissue Adhesive,Fibrin Adhesive,Fibrin Glue,Fibrin Sealant System,Fibrinogen Adhesive,Beriplast,Crosseal,Fibrin Klebe System Immuno,Fibrin Seal,Fibrin Sealant,Fibrin Sealant, Human,Tisseel,Tissel,Tissucol,Transglutine,Adhesive, Fibrin,Adhesive, Fibrin Tissue,Adhesive, Fibrinogen,Glue, Fibrin,Human Fibrin Sealant,Seal, Fibrin,Sealant System, Fibrin,Sealant, Fibrin,Sealant, Human Fibrin,Tissue Adhesive, Fibrin

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