In vivo tissue engineering of adipose tissue for reconstructive surgery

我们能够在大鼠和小鼠中将血管化组织在植入的塑料室中生长至预定的大小和形状（NHMRC项目资助01-03; #145782; CIA莫里森）。这种生长的基础是血管从血管束或血管环的表面发芽，随后是结构分子的合成和周围细胞迁移到血管化网络中以形成稳定的组织。与其他组织工程的体内模型不同，该组织自发生长并且是密集血管化的，使得能够连续生长并通过手术转移到身体的另一部分或另一动物。在上述NHMRC资助的更新申请中，我们建议将这些发现导向血管化脂肪组织的发展，这将是重建手术的理想选择，作为稳定的惰性组织填充物。迄今为止，我们在体内生长脂肪组织的努力已经确定了4个主要要求：脂肪前体细胞来源;指导性基底膜基质（可能包括生长分化因子）;组织可以生长的空间;稳定的血液供应。我们将在这里专注于优化前体细胞来源和指导性基质，以在我们的组织工程室中产生的血液供应周围产生血管化脂肪组织。我们已经发现Matrigel，一种富含基底膜成分的小鼠肿瘤衍生基质，对脂肪生长具有指导意义，并且还将建立在肌肉或脂肪组织可以为这一过程提供适当前体细胞的初步观察基础上。最后，我们建议调整和扩大血管化脂肪组织室的猪，在人类使用的一步，并评估其可移植性和寿命。我们的工作的临床应用是生产乳房再造组织和脂肪填充，用于创伤，先天畸形，衰老和癌症手术造成的轮廓畸形，特别是乳房再造。

We are able to grow vascularised tissue in implanted plastic chambers to a predetermined size and shape in the rat and mouse (NHMRC Project Grant 01-03; #145782; CIA Morrison). The basis of this growth is blood vessel sprouting from the surface of the vessel bundle or loop, followed by synthesis of structural molecules and the migration of surrounding cells into the vascularised network to form a stable tissue. Unlike other in vivo models of tissue engineering, the tissue grows spontaneously and is densely vascularised, enabling continuous growth and surgically transfer to another part of the body, or to another animal. In this renewal application of the above NHMRC grant, we propose to direct these findings towards the development of vascularised fat tissue which would be ideal for reconstructive surgery as a stable, inert tissue filler. Our efforts to grow fat tissue in vivo to date have identified 4 major requirements: a fat precursor cell source; an instructive basement membrane matrix (which may include growth-differentiation factors); space into which the tissue can grow; a stable blood supply. We will focus here on optimising the precursor cell source and instructive matrix to generate vascularised fat tissue around the blood supply we can engender in our tissue engineering chamber. We have found Matrigel, a mouse tumor-derived matrix rich in basement membrane components, to be instructive for growing fat, and will also build on preliminary observations that either muscle or fat tissue can provide the appropriate precursor cells for this process. Finally we propose to adapt and upsize the vascularised fat tissue chamber to the pig, in a step towards human use, and assess its transplantability and longevity. The clinical application of our work is to produce breast reconstruction tissue and lipo filling for contour deformities resulting from trauma, congenital deformity, ageing and cancer surgery, particularly breast reconstruction.