Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets

Abstract

IntroductionBone marrow (BM) is a complex tissue containing hematopoietic progenitor cells and a connective-tissue network of stromal cells. Marrow stroma includes a subpopulation of undifferentiated cells that are capable of becoming one of a number of phenotypes, including bone and cartilage, tendon, muscle, fat, and marrow stromal connective tissue that supports hematopoietic cell differentiation. 1,2 These cells are referred to as mesenchymal stem cells (MSCs), since they are known to have capacity of proliferation and differentiation into the mesenchymal lineage. Due to their potential for differentiation into different tissues, MSCs have emerged as a promising tool for clinical applications such as tissue engineering and cell and gene therapy. [3][4][5] Several reports underline the ability of MSCs to migrate. [6][7][8][9][10][11][12][13] MSCs are thought to migrate in the bloodstream to seed new sites of hematopoiesis and to various tissues during embryonic and fetal development. 14,15 MSCs are present in large numbers in human blood from at least 7 weeks' gestation and they persist until approximately 12 weeks' gestation. 14 Although circulating MSCs decrease after 12 weeks, there is evidence that a very lowfrequency population of circulating multipotent nonhematopoietic cells resembling the classical MSCs persist through to adult life. [16][17][18] MSCs migrate efficiently to hematopoietic tissues (BM and spleen) after transplantation in some experimental animal models, 19,20 whereas reports of BM homing in humans are inconsistent. [21][22][23][24][25][26] Of particular interest for tissue remodeling, intravenous delivery of MSCs results in their specific migration to a site of injury. [6][7][8]10,27 This ability of implanted MSCs to seek out the site of tissue damage has been demonstrated in bone or cartilage fracture, 28 myocardial infarction, 8,29 and ischemic cerebral injury. 6,10,11 Because MSCs have been shown to give rise to many tissues (such as bone, cartilage, fat, endothelia, muscle, brain, and pancreatic islet cells 30,31 ), migrating MSCs may represent a source of pluripotent cells that are constantly available for the repair of damaged organs. The mechanisms that guide homing of implanted cells are unclear. In this study, we examined the role of chemokines and their receptors in the migration of human MSCs. Moreover the interaction between human pancreatic islets and MSCs was investigated as a model of tissue cross talk. Material and methods Human bone marrow mesenchymal stem cell cultureHuman bone marrow mesenchymal stem cells (BM-MSCs) were obtained from Cambrex (Baltimore, MD). There were 3 different batches used for the study. Before use, the cells were analyzed for morphology, marker For personal use only. on May 11, 2018. by guest www.bloodjournal.org From expression, and osteogenic differentiation. All batches used had a fibroblastlike morphology in culture, were homogeneously CD73 ϩ , CD105 ϩ , HLA I ϩ , ␣V␤3 ϩ , ␣V␤5 ϩ , CD34 Ϫ , CD45 Ϫ , CD117 Ϫ , CD31 Ϫ , HLAII Ϫ , CD18 Ϫ , CD80...

Streptozotocin-induced partial beta cell depletion in nude mice without hyperglycaemia induces pancreatic morphogenesis in transplanted embryonic stem cells

“…Future studies will focus on identification of factors produced by the injured pancreas. In addition, it will be important to characterise the response of putative adult beta stem cell types, such as bone marrow-derived mesenchymal stem cells [26] and intra-pancreatic stem cells [27,28], to stimuli produced by the STZ-injured pancreas. This may be a valuable system for understanding the mechanisms of beta cell neogenesis in the adult and for identification of regenerative factors for use in tissue engineering in vitro.…”

Human platelet‐rich plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells

“…11,27 In recent years, special attention has been drawn to chemokines that stimulate the migration of human bone marrow-derived mesenchymal stem cells. 12,28,29 CSP that were used in the present study are actively recruited by PRP as shown here and by human synovial fluid containing the chemokines CCL25, CXCL10, and XCL1 that stimulate CSP migration in 96-well chemotaxis assays. 21,30 Therefore, it is most likely that PRP, respectively its particular growth factors and chemokines independently or synergistically may enhance the migration of human subchondral progenitor cells.…”

Immunoregulatory function of mesenchymal stem cells

“…MSC can also produce a variety of growth factors, cytokines, chemokines and proteases that are likely to play a role either in their immunomodulatory or in their migratory function [29][30][31]. In this respect, MSC have been shown to express a restricted pattern of chemokine receptors, including CXCR4, allowing them to migrate to tissues upon specific chemotactic triggers [32][33][34][35]. These features are likely to represent the basis for MSC homing to multiple organs where they undergo a program of tissue-specific differentiation [36].…”