Induced Pluripotent Stem Cells and Their Future Therapeutic Applications in Hematology

Abstract

Reprogramming of iPSCs should have the following requirements: (1) species such as humans or mice, (2) cell type such as fibroblasts or blood cells, (3) factor or chemical such as protein, gene or valproic acid, (4) vector such as retrovirus or lentivirus, and (5) diseases with specific genetic mutations [6,7,9]. DNA and non-DNA methods have been employed in induction and programming of iPSCs (Table 4) [4-9]. The following genes have been used in inducing PSCs: Oct 3/4, Sox2, Klf4, C-Myc, Nanog, LIN 28, Glis 1 and REX 1 [3,4,7]. Also, a long list of agents or vectors have been used in iPSC programming and these include: single or multiple transient transfections, excisable and nonintegrating vectors, proteins and direct protein transduction, plasmid and episomal vectors, minicircle DNA, modified RNA, RNA-based Sendai viruses, mRNA-based transcription factor delivery, microRNA transfections, artificial chromosome vectors, chemical compounds and small molecule compounds. These agents have been reported to improve safety and efficacy of the reprogramming process [5,7]. Small molecule compounds have recently been utilized to generate mouse iPSCs from

Introductory Chapter: Update on Mesenchymal and Induced Pluripotent Stem Cells

“…Human iPSCs resemble human ESCs in many aspects including morphology, proliferation, differentiation potential, and pluripotency markers, but the epigenetic characteristics of human iPSCs are rather distinct [1,2,5,61]. Although the utilization of iPSCs can avoid the obstacles and ethical concerns that limit the use of human ESCs, clinical application of human iPSCs still has a number of disadvantages that include chromosomal instability and tumorigenic potential, thus raising questions about the safety of their clinical utilization, and low reprogramming efficiency in addition to other concerns about their reproducibility for laboratory applications in disease modelling and drug screening [1,3,5,61,62].…”

“…In 2006, Takahashi and Yamanaka were the first scientists to generate mouse iPSCs from dermal fibroblasts through retroviral-mediated ectopic expression of the four genes: OCT4, SOX2, KLF4, and c-MYC [1,3,4,63]. Since this discovery, iPSCs have been used in many research and clinical trials, including disease modelling; drug toxicity as well as drug discovery; and regenerative medicine [3][4][5].…”

“…Reprogramming of iPSCs should have the following crucial requirements: species such as human or mouse; cell type such as blood cell or fibroblast; factor, drug, chemical, or other protein molecules such as miRNA, DNA modifying agent, NANOG, or LIN28; vector such as retrovirus or lentivirus; and disease with specific genetic mutation [1,4,5,64].…”

“…Several studies using human iPSC-MSCs and their exosomes in human and animal studies have shown that transplantation of these cells can produce protection of the liver against hepatic ischemia; reduction in the volume of brain infarction and preservation of neurological function after acute intracranial hemorrhage; prevention of osteonecrosis of femoral head by promotion of local angiogenesis and prevention of bone loss; facilitation of cutaneous wound healing by promotion of collagen synthesis and angiogenesis; and modulation of differentiation and function of DCs in order to support their clinical application in DC-mediated immune disorders [69][70][71][72][73]. Thus, MSCs and iPSCs may reshape the future of medical therapeutics and may eventually become curative for several chronic and intractable medical illnesses [2,4,5].…”

“…Stem cells are a subset of biological cells in the human body that are capable of self-renewal, tissue repair, differentiation, and division into different cell lineages [1][2][3]. Based on their origin and potency, stem cells are divided into either (1) embryonic and adult (non-embryonic) stem cells or (2) unipotent, oligopotent, totipotent, multipotent, and pluripotent stem cells [1,2,4,5]. Multipotent or adult stem cells include mesenchymal stem cells (MSCs), while pluripotent stem cells include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) [5].…”