Hindawi Publishing Corporation Bone Marrow Research Volume 2011, Article ID 353878, 8 pages doi:10.1155/2011/353878 Review Article Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche Tian Li and Yaojiong Wu Life Science Division, Graduate School at Shenzhen, Tsinghua University , Shenzhen L406A, China Correspondence should be addressed to Yaojiong Wu, wu.yaojiong@sz.tsinghua.edu.cn Received 31 May 2011; Revised 26 July 2011; Accepted 26 July 2011 Academic Editor: Joseph H. Antin Copyright © 2011 T. Li and Y. Wu. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation. 1. Introduction Hematopoietic stem cells (HSCs) are rare cells residing in the bone marrow (BM; 1 in 104 to 1 in 108 of BM nucle- ated cells), and they are progenitors that become progres- sively restricted to several or single lineages. These progen- itors yield blood precursors devoted to unilineage diﬀeren- tiation and the production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells (mono- cyte/macrophage and neutrophil), and lymphocytes [1, 2]. CD34 surface antigen (CD34+) is commonly used as a marker to identify and quantify the population of progenitor cells [3], according to which, sorting HSCs from BM, periph- eral blood (PB), and umbilical cord (UC)/placenta blood is relatively simple and practical [2, 4–6]. Human HSCs are known to exhibit CD34+, Thy1+, CD38lo/−, Ckit−/lo, CD105+, and Lin− phenotype. However, there is no general agreement on the association between any combination of these antigenic properties and function of stem cells [3, 6]. HSCs depend on their microenvironment, the niche, for regulating self-renewal and diﬀerentiation [7]. For instance, the disruption of BMP pathway can increase the numbers of osteoblasts and HSCs [8, 9], and the chemokine CXCL12 regulates the cyclical release and the migration of HSCs [10, 11]. Activation of β-catenin enforces HSCs enter cell cycle, thus leading to exhaustion of the long-term stem cell pool [12–14]. These ﬁndings suggest that signaling pathways and cellular interactions regulate the BM niche for HSCs. Besides, hypoxia regulate hematopoiesis in BM by maintaining important HSC functions and the interplay between HSCs and neighboring cells [15, 16]. Plating studies indicate that mesenchymal stem cells (MSCs) are present as a rare population of cells in the BM. They represent approximately 0.001% to 0.01% of the nucleated cells, about 10-fold less abundant than HSCs, but MSCs can be readily grown in culture [17]. Though predominantly residing in the BM, MSCs also present similar but not identical features in many other tissues such as blood, placenta, dental pulp, and adipose tissue. MSCs have the potential to diﬀerentiate into multiple phenotypes such as osteoblasts, chondrocytes, adipocytes, neural cells, and probably other cell lineages [18–21]. International Society for Cellular Therapy (ISCT) has provided the following minimum criteria for deﬁning multipotent mesenchymal stromal cells as follows: plastic-adherent under standard culture conditions; express CD105, CD73, and CD90 and lack expression of CD45, CD34, CD14, or CD11b, CD79 or CD19 and HLA-DR, and must diﬀerentiate into osteoblasts, adipocytes, and chondroblasts in vitro [22]. BM has received the most attention because it carries MSCs as well as HSCs. Evidence indicates that MSCs are key component of the HSC niche in the BM where these two distinct stem cell populations arrange closely, ensuring hematopoietic and skeletal homeostasis [18]. MSCs interact with HSCs, secreting chemokines that contribute to HSC niche and support long-term growth of HSCs [23, 24].