In vivo tissue engineering of adipose tissue for reconstructive surgery

我们能够在大鼠和小鼠体内将植入的塑料腔中的血管组织培养成预定的大小和形状(NHMRC Project Grant 01-03；#145782；CIA Morison)。这种生长的基础是血管从管束或环的表面萌发，随后结构分子的合成和周围细胞的迁移进入血管网络，形成稳定的组织。与其他体内组织工程模型不同，组织会自发生长，并被密集地血管化，从而能够持续生长并通过手术转移到身体的另一部分或另一种动物。在上述NHMRC拨款的续期申请中，我们建议将这些发现用于血管脂肪组织的开发，作为一种稳定、惰性的组织填充物，这将是重建手术的理想选择。到目前为止，我们在体内培养脂肪组织的努力已经确定了四个主要要求：脂肪前体细胞来源；具有指导性的基底膜基质(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。在这里，我们将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血液供应周围的血管脂肪组织。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作用，并将建立在初步观察的基础上，即肌肉或脂肪组织可以为这一过程提供适当的前体细胞。最后，我们建议将血管脂肪组织腔适应和扩大到猪身上，这是人类使用的一步，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重建组织和脂肪填充，用于治疗因创伤、先天性畸形、衰老和癌症手术，特别是乳房重建而导致的轮廓畸形。

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.