MHC II gene knockout in tissue engineering may prevent immune rejection of transplants

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Summary

The repair and reconstruction of tissue defects and organ loss are severe problems, and many patients are eager to find avenues to these matters. Up until now, the number of methods used to repair tissue defects has increased, but all of these have their own advantages and inconveniences, and do not seem to have been optimized. The development of tissue engineering offers new hopes to patients with tissue defects. To regenerate tissues and organs, we first need a source of seed cells. However, the sources of autologous cells are restricted, cell number is small, and xenogenic cells result in immunological rejections. Major histocompatibility complex (MHC) polymorphism is a key factor in tissue grafts. MHC II, in particular, is associated with allogeneic transplantation. We hypothesize that if we knock-out the MHC II gene of mesenchymal stem cells (MSCs) in vitro, these cells would not express MHC II molecules, and rejection problems will be solved. Accordingly, the industrialization of tissue engineering will be feasible, and products of tissue engineering will be utilized widely for any clinical treatments.

Introduction

Tissue repair and reconstruction are common clinical topics, and involve difficult techniques and methods. The current methods used have their advantages and disadvantages, but none has been completely satisfying. With the ongoing advances in cell biology and engineering, tissue engineering has now become the new term for the use of cells and scaffolds to make tissues and organs in vitro. The seed cells are an indispensable part of the engineering tissue or organ. Nowadays, xenogenic stem cells are mostly used as seed cells. However, the immunogenicity of xenogenic stem cells often induces immunological rejection and failure of tissue regeneration. This is already seen as the key problem for the clinical application of tissue engineering. In this paper, we hypothesize that if MHC II was not expressed in the xenogenic stem cells, then the immune reactions resulting from MHC II could be blocked; and xenogenic stem cells could eventually be used in tissue engineering without any restrictions. We introduce, here, some advances in tissue engineering, immunity, and gene therapy, and prove the practicality and feasibility of our hypothesis.

Section snippets

Repair and reconstruction of tissue defects

Tissue defects are common and complicated. Several approaches exist to solve them. These include the use of autografts of vascularized valves [1], [2], [3], bone autografts [4], allografts [5], [6], and succedaneum [7], [8], [9]. However, none of these restorative procedures is totally satisfying. Autografts without histocompatibility problems and rejection reactions from the postgrafts, usually result in complications in the donor [10], [11], and are hard to source. Allografts or heteroplasms

Tissue engineering

Tissue engineering refers to the application of principles and methods of engineering and life sciences towards the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues, and the development of biological substitutes to restore, maintain, or improve tissue function. The starting point of any tissue engineering method is the harvest of cells, followed by the culture of cells and their amplification in vitro to provide a “cell bank”. Hence,

Major histocompatibility complex

The major histocompatibility complex (MHC) is a gene dense region found in all jawed vertebrates examined to date. The MHC family contains a high percentage of immune genes, in particular, genes involved in antigen presentation, which are generally highly polymorphic. MHC is a member of the immunoglobulin gene superfamily. Major histocompatibility antigens encoded by the MHC gene can result in intense tissue rejection reactions, and those are involved in allogeneic grafts [19]. At present, the

Gene knockout

Gene knockout manipulation which has been developed since the end of 1980s, is a novel technique in tissue engineering. Gene knockout is a kind of experimental technology, which makes use of the principle of DNA homologous recombination. It involves the knockout of a known gene or substitutes another similar sequence of a particular gene to target a gene of interest. Gene knockout can stop gene expression, allows the insertion of a new gene sequence, and induces a specific point mutation. Gene

Hypothesis

Based on the above studies, we hypothesize that the knockout of the MHC II gene in allogeneic seed cells will completely result in the absence of an immunological rejection response caused by allogeneic MHC II. It could be an ideal method to resolve the problem of restricted sources of seed cells.

This will provide the theoretical and experimental foundation for the industrialization of such a system, and the clinical use of tissue engineered materials. This work provides a new field of

Acknowledgement

Sources of support: Funding from Outstanding Young Academic Leaders of Sichuan Province (06ZQ026-008) and National Natural Foundation of China (30100210 and 30572051).

References (30)

  • D.M. Ehrler et al.

    The use of allograft bone in lumbar spine surgery

    Clin Orthop Relat Res

    (2000)
  • T. Ozaki et al.

    Reconstruction of tibia by ipsilateral vascularized fibula and allograft-12 cases with malignant bone tumors

    Acta Orthop Scand

    (1997)
  • B.R. Halliday et al.

    Femoral impaction grafting with cement in revision total hip replacement. Evolution of the technique and results

    J Bone Joint Surg Br

    (2003)
  • R. Hu et al.

    Bone graft harvest site as a determinant of iliac crest strength

    Clin Orthop Relat Res

    (1995)
  • S. Giboson et al.

    Allograft versus autograft in Instrumented posterolateral lumber spinal fusion: a randomized control trial

    Spine

    (2002)
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