Living Bone Allotransplants Survive by Surgical Angiogenesis Alone: Development of a Novel Method of Composite Tissue Allotransplantation

Larsen, Mikko; Pelzer, Michael; Friedrich, Patricia F.; Wood, Christina M.; Bishop, Allen T.
February 2011
Journal of Bone & Joint Surgery, American Volume;2/2/2011, Vol. 93-A Issue 3, p261
Academic Journal
Background: Segmental bone defects pose reconstructive challenges. Composite tissue allotransplantation offers a potential solution but requires long-term immunosuppression with attendant health risks. This study demonstrates a novel method of composite-tissue allotransplantation, permitting long-term drug-free survival, with use of therapeutic angiogenesis of autogenous vessels to maintain circulation. Methods: Ninety-three rats underwent femoral allotransplantation, isotransplantation, or allografting. Group-1 femora were transplanted across a major histocompatibility complex barrier, with microsurgical pedicle anastomoses. The contralateral saphenous artery and vein (termed the AV bundle) of the recipient animal were implanted within the medullary canal to allow development of an autogenous circulation. In Group 2, allotransplantation was also performed, but with AV bundle ligation. Group 3 bones were frozen allografts rather than composite-tissue allotransplantation femora, and Group 4 bones were isotranspiants. Paired comparison allowed evaluation of AV bundle effect, bone allogenicity (isogeneic or allogeneic), and initial circulation and viability (allotransplant versus allograft). Two weeks of immunosuppression therapy maintained blood flow initially, during development of a neoangiogenic autogenous blood supply from the AV bundle in patent groups. At eighteen weeks, skin grafts from donor, recipient, and third-party rats were tested for immunocompetence and donor-specific tolerance. At twenty-one weeks, bone circulation was quantified and new bone formation was measured. Results: Final circulatory status depended on both the initial viability of the graft and the successful development of neoangiogenic circulation. Median cortical blood flow was highest in Group 1 (4.6 mL/min/100 g), intermediate in Group 4 isotransplants (0.4 mL/min/100 g), and absent in others. Capillary proliferation and new bone formation were generally highest in allotransplants (15.0%, 6.4 μm3/μm2/yr) and isotransplants with patent AV bundles (16.6%, 50.3 μm3/μm2/yr) and less in allotransplants with ligated AV bundles (4.4%, 0.0 μm3/μm2/yr) or allografts (8.1%, 24.1 μm3/μm2/yr). Donor and third-party-type skin grafts were rejected, indicating immunocompetence without donor-specific tolerance. Conclusions: In the rat model, microvascular allogeneic bone transplantation in combination with short-term immunosuppression and AV bundle implantation creates an autogenous neoangiogenic circulation, permitting long-term allotransplant survival with measurable blood flow. Clinical Relevance: These methods may allow future composite-tissue allotransplantation of bone without the appreciable health risks that are associated with long-term immunosuppression or immune tolerance induction.


Related Articles

  • Adoptive Infusion of Tolerogenic Dendritic Cells Prolongs the Survival of Pancreatic Islet Allografts: A Systematic Review of 13 Mouse and Rat Studies. Guixiang Sun; Juan Shan; Youping Li; Yanni Zhou; Yingjia Guo; Wenqiao Wu; Tong Yang; Mengjuan Xia; Li Feng // PLoS ONE;Dec2012, Vol. 7 Issue 12, p1 

    Objective: The first Phase I study of autologous tolerogenic dendritic cells (Tol-DCs) in Type 1 diabetes (T1D) patients was recently completed. Pancreatic islet transplantation is an effective therapy for T1D, and infusion of Tol-DCs can control diabetes development while promoting graft...

  • Induction of Foxp3-Expressing Regulatory T-Cells by Donor Blood Transfusion Is Required for Tolerance to Rat Liver Allografts.  // PLoS ONE;2009, Vol. 4 Issue 11, p1 

    The article discusses a study conducted to define kinetics, phenotype and suppressive function of the regulatory cells induced by Donor-Specific Blood Transfusion (DST) alone or in combination with liver allograft transplantation (LTx). It has been informed that DST in rat liver allograft...

  • Immune tolerance of epithelium-denuded-cryopreserved tracheal allograft. Hysi, Ilir; Wurtz, Alain; Zawadzki, Christophe; Kipnis, Eric; Jashari, Ramadan; Hubert, Thomas; Ung, Alexandre; Copin, Marie-Christine; Jude, Brigitte // European Journal of Cardio-Thoracic Surgery;Jun2014, Vol. 45 Issue 6, pe180 

    OBJECTIVES Animal and clinical studies have demonstrated the feasibility of tracheal allograft transplantation after a revascularization period in heterotopy, thus requiring immunosuppressive therapy. Given the key role of the respiratory epithelium in the immune rejection, we investigated the...

  • Toxicity and Carcinogenicity Studies of Ginkgo biloba Extract in Rat and Mouse: Liver, Thyroid, and Nose Are Targets. Rider, Cynthia V.; Nyska, Abraham; Cora, Michelle C.; Kissling, Grace E.; Smith, Cynthia; Travlos, Gregory S.; Hejtmancik, Milton R.; Fomby, Laurene M.; Colleton, Curtis A.; Ryan, Michael J.; Kooistra, Linda; Morrison, James P.; Chan, Po C. // Toxicologic Pathology;Jul2014, Vol. 42 Issue 5, p830 

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and...

  • Regulatory Forum Opinion Piece: Long-term Animal Bioassays: Is the End Near?*. Gori, Gio Batta // Toxicologic Pathology;Jul2013, Vol. 41 Issue 5, p805 

    Long term bioassays in animals cannot reliably forecast unknown potential but distant human risks, and especially cancer risks. The genetic, anatomic, physiologic, behavioral and environmental adaptations of rats and mice - the officially prescribed animals - are not relevant to humans. Even...

  • Feasibility of FRAX for Prediction of Osteoporotic Vertebral Fractures in Korea. Gwang-Young So; Kyung-Ho Park; Dea-Hyun Yoon; Ji-Hoon Ryu; Yong-Soo Choi // Asian Spine Journal;Mar2012, Vol. 6 Issue 1, p22 

    Study Design: Retrospective study. Purpose: To assess the feasibility and limitations of fracture risk assessment tool (FRAX) for osteoporotic vertebral fractures in the Korean population. Overview of Literature: The FRAX algorithm is country specific and uses clinical risk factor data to...

  • Elders: Eat Protein for Strong Bones.  // Agricultural Research;Sep2001, Vol. 49 Issue 9, p23 

    Deals with the importance of dietary protein in maintaining strong bones in the elderly. Background on a research on protein intake; Association between animal protein and bone loss protection.

  • Appreciation of Osteoporosis Among Men with Hyperparathyroidism. Naveen Ballem; Andrew Greene; Rikesh Parikh; Eren Berber; Allan Siperstein; Mira Milas // Endocrine Practice;Oct2008, Vol. 14 Issue 7, p820 

    Objective: To define the scope of bone disease among men referred for parathyroidectomy and to document bone density screening trends in this high-risk population.Methods: Clinical data were analyzed from a prospectively maintained database of 1000 patients undergoing parathyroidectomy for...

  • BMD: The problem. Heaney, Robert P. // Osteoporosis International;Sep2005, Vol. 16 Issue 9, p1013 

    Comments on the importance of bone mineral density in the identification and treatment of osteoporosis. Assessment of the changes in bone size and mass over time in a cohort of milk-avoiding children; Analysis on the extent of bony deficit; Comparison of bone variables between individuals.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics