Stem cells and adipose tissue engineering

Abstract

A large proportion of the plastic and reconstructive surgical procedures performed each year are to repair soft tissue defects that result from traumatic injury, tumor resection, and congenital defects. These defects typically result from the loss of a large volume of adipose tissue. To date, no ideal filler material which is successful in all cases has been developed. Additionally, the success of using autologous fat tissue grafts to repair soft tissue defects has been limited. Researchers are thus investigating strategies to engineer volumes of adipose tissue that may be used in these cases. A necessary component for engineering a viable tissue construct is an appropriate cell source. Attempts to engineer adipose tissue have involved the use of preadipocytes and adipocytes as the base cell source. Increased interest surrounding the research and development of stem cells as a source of cells for tissue engineering has, however, led to a new path of investigation for developing adipose tissue-engineering strategies. This manuscript serves as a review of the current state of adipose tissue-engineering methods and describes the shift toward tissue-engineering strategies using stem cells.

Introduction

A soft tissue defect is generally defined as a large tissue void within the subcutaneous fat layer of the skin that often results in a change in the “normal” tissue contour [1]. Restoration of natural tissue function is not often the primary goal in reconstruction; rather, restoration of the soft tissue aesthetic function is targeted in order to minimize the anxiety and negative psychological feelings associated with disfigurement. Millions of plastic and reconstructive surgical procedures are performed each year to repair soft tissue defects that result from traumatic injury (i.e., significant burns), tumor resections (i.e., mastectomy and carcinoma removal), and congenital defects [2]. The American Society of Plastic Surgeons reported that over 5 million reconstructive procedures were performed in 2004, approximately 4 million of which were due to tumor removal [3]. Strategies to repair soft tissue defects, e.g. breast reconstruction procedures, collagen injections, and the use of autologous tissue transfers (i.e. free fat tissue grafts and tissue flaps) [4], [5], include the use of implants and fillers [6], [7]; however, there is likely no single filler material that will satisfy all clinical needs. Excess amounts of adipose tissue are found all over the human body, and may be readily obtained through liposuction and transplanted to a target location. The use of autologous fat tissue to repair soft tissue defects is logical in its approach, but the use of this method has not been consistently successful in patients [1], [8], [9], [10]. When autologous fat tissue is transplanted from one location to the defect site, the common occurrence is significant resorption of the transplanted tissue over time, resulting in 40–60% of the graft volume loss. One proposed reason for tissue resorption is lack of sufficient revascularization of the tissue following transplantation to a new location [1], [8], [11]. The fat grafts never acquire sufficient vascularity, so centralized graft blood flow is not adequate for long-term survival of the tissue, and often leads to tissue resorption [10]. This insufficient tissue vascularization limits the supply of oxygen and nutrients to the tissue, limiting the chances for long-term tissue viability [12]. Tissue-engineering strategies are thus being investigated to develop methods for generating adipose tissue.

The primary goal of tissue engineering is to regenerate healthy tissues or organs for patients in need, thus eliminating the need for tissue or organ transplants and mechanical devices. With organ and tissue transplants, immunological rejection is often a primary concern for patients receiving donated tissues. Tissue-engineering strategies are suggested to eliminate these concerns [13]. Specifically, healthy cells taken from a patient may be cultured in a laboratory to attain a larger number of healthy cells. These cells may then be seeded onto a scaffold that will support cell growth and proliferation. The cell-covered scaffold may then be implanted into the patient at the needed site. As the cells grow, the scaffold material degrades or absorbs, and ultimately, a new tissue mass remains [14], [15]. In this method of scaffold-guided tissue regeneration, scaffolds are used as support structures that provide a surface for cells to adhere to, and that provide a shape for the tissue that the construct is mimicking [8], [16]. Tissue-engineering methods are being used to develop a wide range of tissues, including bone, skin, cartilage, vascular, and adipose tissues [17]. The development of adipose tissue-engineering strategies will be essential in the restoration of tissue at soft tissue defect sites.