Submit Manuscript | http://medcraveonline.com Abbreviations: iPSC, induced pluripotent stem cells; HSC, hematopoietic stem cells; IL, interleukin; GM-CSF, granulocyte-ma- crophage colony-stimulating factor Introduction Recent literature has demonstrated the possibility of deriving hematopoietic stems cells from induced pluripotent stem cells by co- culturing the iPSCs with OP9 stromal cells. Although HSCs can be derived from iPSCs, researchers continue to investigate the molecular factors that play important roles in this process. If HSCs can be effectively developed with improved yields, the medical community may potentially reduce the number of blood transfusions that leukemia patients would have to undergo. An overall review of the current literature will be critical in further understanding hematopoiesis and the engraftment potential of iPSCs in leukemia patients. Discussion iPSC differentiation techniques and hematopoiesis Hematopoiesis is the process by which the cellular components of blood are formed- usually during development. In vertebrates, there are two documented waves of hematopoiesis; the primitive wave and the defnitive wave. 2 The frst wave, the primitive wave, occurs during early embryonic development and gives rise to the erythrocytes and macrophages. This wave is integral to development, as it provides the red blood cells necessary for tissue oxygenation throughout the rest of development. This stage is transient, and later gives rise to the defnitive wave of hematopoiesis. Within the defnitive wave, which continues much throughout adulthood, the entire lineage of blood cells are able to be formed, including red blood cells, white blood cells, platelets. Among the various types of cells, multipotent HSCs are generated and are harbored mostly within the bone marrow. 3 In 2006, researchers at Kyoto University in Japan identifed a specialized protocol that would induce adult cells to be “reprogrammed” into cells that were pluripotent and could be differentiated into virtually any cell type. 4 The discovery of induced pluripotent stem cells (iPSCs) led to new avenues of investigation in the innovative feld of regenerative medicine, with the potential to provide personalized medical therapy and circumvent issues such as graft versus host disease. These cells also managed to avoid some of the ethical issues that belie regular stem cells, as they were developed from each individual patient’s own cells - a further avenue exploring personalized stem cell therapy. In a 2011 study led by Salvagiotto et al., 5 it was shown that a single matrix protein in concert with hypoxic conditions were suffcient to effciently generate pluripotent hematopoietic stem cell progenitors in vitro. Nine lines of iPSC cells were tested to examine which condition would provide the most robust amount of clinical grade progenitors that were induced from pluripotent cells. Hypoxic conditions were used to mimic an early embryonic environment in which HSC progenitor production is often robust. After initiating the protocol and co-culturing of iPSCs with the matrix protein BMP4-VEGF-bFGF, a 5% oxygen tension was added in order to mimic hypoxic conditions in the embryo. Hematopoietic progenitors were then identifed with fow cytometry to count the CD34+ cells, which is a marker that characterizes progenitor cells. The study concluded that, although the clinical introduction of this protocol would be relatively easy due to a plausible switchover in xenophobic conditions, the protocol must be investigated in further detail to see whether higher yields of hematopoietic progenitors could be achieved. Co-culturing of OP9 mouse bone marrow (BM) stromal cells with iPSCs is as another effcient method that has generated higher yields of hematopoietic progenitors. 6 This technique, although typically used to differentiate hematopoietic embryonic stem cells (hESCs), has proven to be effective with iPSCs and can be executed with or without Adv Tissue Eng Regen Med Open Access. 2017;3(1):296‒298 296 © 2017 Amedeo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Optimization of hematopoietic induction from induced pluripotent cells Volume 3 Issue 1 - 2017 Michael Amedeo, Prableen K Chowdhary, Aria Jalalian, Wei Chen Lai, Amil Sahai, George Thomas, Akhil Uppalapati, Farah Vejzagic, Nam Sun Wang Department of Chemical and Biomolecular Engineering, University of Maryland, USA Correspondence: Nam Sun Wang, Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD 20742, USA, Tel 301-405-1910, Fax 301-405-0523, Email nsw@umd.edu Received: September 13, 2017 | Published: October 06, 2017 Abstract Acute myeloid leukemia is the most aggressive form of leukemia that results in immature hematopoietic stem cells (HSCs) that are unable to undergo normal hematopoiesis. Currently, the literature has shown that one can derive HSCs from induced pluripotent stem cells (iPSCs) by co-culturing iPSCs with OP9 stromal cells.1 While this is an effective method of generating HSCs, the mechanism behind this induction of hematopoiesis is not fully understood yet. It remains unclear whether direct contact of OP9 cells is necessary to induce hematopoietic differentiation or if simply the proteins or transcription factors that OP9 cells secrete are sufficient. Our review examines the current literature on the mechanism behind hematopoiesis involving the OP9 co-culturing methodology and the isolation of molecular components that may be responsible for induced hematopoiesis. Significant OP9 excretions that may play a role in hematopoietic induction are: Lhx2, Hoxb4, Bmi-1, IL-7, and AML1-ETO Fusion Protein. In this paper we explore the characteristics of these proteins and their potential applications towards the optimization of hematopoietic induction. Keywords: acute myeloid leukemia, ipsc, hematopoiesis, hematopoietic stem cells, op9 coculture, stem cells, cell culture Advances in Tissue Engineering and Regenerative Medicine Mini Review Open Access