Recent Patents on Regenerative Medicine 2011, 1, 195-206 195 2210-2973/11 $100.00+.00 © 2011 Bentham Science Publishers Ltd. Recent Advances in Hematopoietic Stem Cell-Mediated Regeneration Suman Kanji, Vincent J. Pompili and Hiranmoy Das* Cardiovascular Stem Cell Research Laboratory, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USA Received: November 22, 2010; Accepted: January 17, 2011; Revised: January 19, 2011 Abstract: Hematopoietic stem cells (HSC) are being considered as one of the most potential regimens for regenerative therapy in various disease states and last several decades of research helped us to understand them better regarding the regenerative capabilities of HSC. HSC can be isolated from different sources such as peripheral blood, bone marrow and cord blood. Rigorous scientific investigations on cell surface marker, biology, niche and functionality determined that self-renewal and multi-lineage differentiation capability possessed by HSCs and easy accessibility made them one of the most used stem cells for clinical applications. This review focuses not only on the recent advancement of HSC in restoration of hematopoiesis in different immunological and hematological malignancies but also on the contribution of HSC to vasculogenesis and angiogenesis especially in ischemic conditions in various tissues. We have emphasized about the promise in use of the HSC in regenerative medicine in various preclinical and clinical set-up. Being the first adult stem cell in the history of regenerative medicine, basic biology of HSC is well documented. Several attempts have been made to manipulate the basic biology of HSCs to adjust efficient implementation of HSC in preclinical models. In order to increase the benefit of transplantation effect in clinical practice, large numbers of stem cells were required, which were made possible by expansion of HSC. Here, we discussed in detail the techniques used to manipulate HSC niche and modifications of external stimulating factors to achieve large number of transplantable HSCs. HSCs are also being used as a targeted vehicle for gene delivery discussed in detail. Finally, we have cited some of the important patents, which reflect the breadth of the advances in basic HSC biology, expansion technique, preclinical models and clinical transplantation. Keywords: Cord blood, stem cells, nanofiber, expansion, gene, engineering, overexpression, regeneration. INTRODUCTION The regeneration of injured tissues was reported since the time of Greeks as stories about regeneration are found in Greek mythology. The emerging evidences have shown that the presence of tissue specific stem cells can be isolated from different tissues and organs [1-3]. Self-renewal is the key feature of tissue specific stem cells, however, it can differentiate into specific cell type to regenerate a particular organ or tissue according to the need. The number of tissue specific stem cells is insufficient to regenerate tissue or organs after injury. Thus, isolation of tissue-specific stem cells and their transplantation potency in human are under critical investigation. Hematopoietic stem cells (HSCs) are the best charac- terized stem cell population. The presence of HSCs was reported long back, and it was found that a population of bone marrow (BM) cells can generate myeloerythroid colonies in the lethally irradiated host spleens [4]. A delicate balance of self-renewal and differentiation of HSCs is maintained to achieve homeostasis within the BM during normal physiological conditions. During injury or pathophy- siological conditions mitogenic stimulation alters the normal signaling pathways within the stem cell niche, hence it *Address correspondence to this author at the Cardiovascular Stem Cell Research Laboratories, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 460 W. 12 th Avenue, BRT 382, Columbus, Ohio 43210, USA; Tel: (614) 688-8711; Fax: (614) 293-5614; E-mail: hiranmoy.das@osumc.edu induces differentiation of stem cells to meet the regenerative requirements. However, accumulating evidences show that the umbi- lical cord blood (UCB) provides a significant amount of hematopoietic progenitor cells and has become an alterative source for HSC transplantation in various hematopoietic and malignant disorders. Several attempts were made to purify HSCs from BM or UCB for successful transplantation to reduce transplantation related complexities such as edema, aberrant angioma in cardiovascular diseases [5] and to increase engraftment efficiencies in blood related disorders [6]. After successful identification of surface markers, such as CD34, CD133, and their characterization in different preclinical models, HSC transplantation is common in various disease conditions to improve the quality and life expectancy of patients suffering from diverse hematologic and malignant conditions [7, 8]. In this review, we will discuss the hematopoietic and angiogenic potential of HSCs and their obstacles in regenerative therapy. Several approaches were considered to enhance the regenerative efficiencies of HSCs by ex vivo expansion or by transduction of HSC with target gene to overcome these obstacles related to HSC transplantation in clinical practice. HEMATOPOIETIC STEM CELLS IN BLOOD REGENERATION For successful regenerative therapy of HSCs, proper isolation of hematopoietic stem and progenitor cells and their