The Scope of Stem Cell Transplantation in Tissue and Organ Regeneration: Myth or Reality?

Review Article

J Stem Cell Res Transplant. 2014;1(2): 1007.

The Scope of Stem Cell Transplantation in Tissue and Organ Regeneration: Myth or Reality?

Bishi DK and Guhathakurta S*

Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India

*Corresponding author: Guhathakurta S, Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India

Received: August 09, 2014; Accepted: September 15, 2014; Published: September 17, 2014

Abstract

Transplantation of stem cells to regenerate and repair damaged organs offers promising scope for treating various debilitating diseases and is a feasible alternative to organ transplantation, owing to the ability of stem cells to repopulate the engrafted site by differentiation or trans-differentiation. However, before stem cell-based therapies could be transferred to clinic many challenges such as controlling the self-renewal, differentiation efficiency, and integration of engrafted stem cells or differentiated cells to the host milieu need to be optimized. In this review, we summarize strategies that have been used in stem cell-based regenerative medicine and in particular, feasibility of stem cell therapies in restoring damaged tissue and organs.

Keywords: Stem cell; Regeneration; Therapy; Scaffold; Biomaterial; Differentiation

Abbreviations

ES: Embryonic Stem cells; EG: Embryonic Germ Cells; iPSCs: induced Pluripotent Stem Cells; SCT: Stem Cell Therapy; MSC: Mesenchymal Stem Cells; MAPC: Multipotent Adult Progenitor Cells; MIAMI: Marrow-Isolated Adult Multilineage Inducible cells; ADSC: Adipose Derived Mesenchymal Stem Cells; CSCs: Cardiac Resident Stem cells; SPOC: Skeletal Progenitor cells for Cardiomyocytes; ECM: Extracellular Matrix; HCN2: Hyperpolarization-activated Cyclic Nucleotide-gated ion channel 2; SP: Side Population cells; GH: Growth Hormone; FSH: Follicle Stimulating Hormone; LH: Leutinizing Hormone; ACTH: Adrenocorticotropic Hormone; TSH: Thyroid Stimulating Hormone; ABCG2: ATP-Binding Cassette Sub-family G member 2; SJS: Stevens-Johnson Syndrome; LSCD: Limbal Stem Cell Deficiency; OA: Osteoarthritis; ACT: Autologous Chondrocyte Transplantation

Introduction

Tissue regeneration from stem cells is an old concept way back to 1961 by McCulloch and Till when they demonstrated different lineage of blood cells from a common origin of a stem cell [1]. Regenerative capabilities of vertebrates at certain tissue regions have limitations, either they do not regenerate after adult form or regeneration rate is very poor [2]. The more maturation of a cell type happens, the lesser regenerative capability ensues. The best example is myocardial cell repair after myocardial injury from infarction. Whatever extent of damage is produced, 5% recovery of the tissue loss can be expected [3,4]. Greek mythology based liver recovery of Prometheus though stands a scientific basis of replenishment of certain tissue in the body after injury, it is evident that the invertebrates and non-mammalian vertebrates develop this kind of replenishment very fast at every sectors of the body, if limbs are cut they grow their limb. For example, Planarians and non-mammalian vertebrates such as salamanders and teleost fish exhibit an extraordinary ability to regenerate lost body parts much more effectively than mammals [5].

Clinical research has progressed to a great extent towards preventing, diagnosing and managing debilitating diseases. Culture of human stem cells, including embryonic stem (ES) cells, embryonic germ (EG) cells, induced pluripotent stem cells (iPSCs) and adult stem cells provide unique opportunities for studying and understanding molecular basis and pathophysiology of heart diseases, liver failures, diabetes, cancer and diseases of the nervous system. It was widely believed that tissue-specific stem cells are the prime candidates that differentiate into mature cells of the respective tissue. Present status of great advancement in stem cell technology, the information we have is that ES cells have greater capability of producing required tissue provided the same cue is given to them. Derivation of ES cells from early human embryos, and embryonic germ cells and fetal stem cells from aborted fetuses, raise ethical, legal, religious, issues [6]. The recent breakthrough in the field of iPSCs have opened up a new era in the field of stem cell based tissue regeneration, wherein patient-specific stem cells can be generated from mature cells that can regenerate the tissue or organ of interest. Immune rejection posing a major threat to the success of stem cell transplantation, particularly for the embryonic stem cells-derived phenotypes in allogenic recipients due to histoincompatibility [7,8], recent attempts to generate immune-protected ESC-derived allografts [9] garner some hopes for future. Due to the unique immunomodulatory property of suppressing T cell alloreactivity [10], autologous adult stem cell transplantation [11] as well as allogenic mesenchymal stem cell therapy [12] has been successful in clinical trials. Therapeutic potential of iPSCs was questionable due to previous findings reporting immunogenicity of iPSCs-derived teratoma in syngeneic hosts [13]. However, recent reports suggest that syngeneic ‘‘self’’-iPSCs and their derivatives are immunotolerant in the host [14,15] supporting their safer clinical use in cellular therapy. Despite significant progress in the stem cell-based research, the potential uses of stem cells for regenerating human tissue and perhaps organs are the subjects of ongoing public debate.

Various clinical studies have confirmed that adult tissue-specific stem cells exhibits plasticity and differentiate or trans-differentiate to cells of various lineages. As a result, we could envisage experiments converting a single undifferentiated cell or a fertilized egg, into the different cells comprising the organs and tissue of the human body. To think rationally, human being, an advance mammalian species does not have simple mechanism of organ development. Many organs such as heart, liver, kidneys etc. have complex developmental biology. However, it is plausible that organs or tissue with singular or similar cell types can be addressed by stem cells during their loss. In this review, we discuss the feasible strategies using various categories of stem cells combined with biomaterials scaffolds for regeneration of various tissue and organs.

Stem cell based regeneration of various tissue and organs

The stem cells with varying origin such embryonic and adult tissue as well as iPSCs with varying differentiation efficiency have been induced towards specific lineage with the hope of regenerating tissue and organs of interest, by using scaffolds of natural and synthetic origin [16,17]. Major applications of stem cells in regeneration of various functionally important tissues have been depicted in Figure 1 and illustrated in details as follows.

Citation: Bishi DK and Guhathakurta S. The Scope of Stem Cell Transplantation in Tissue and Organ Regeneration: Myth or Reality?. J Stem Cell Res Transplant. 2014;1(2): 1007. ISSN:2381-9065