Human Application of Ex Vivo Expanded Umbilical Cord-Derived Mesenchymal Stem Cells: Enhance Hematopoiesis after Cord Blood Transplantation

Abstract Mesenchymal stem cells (MSCs) have been isolated from venous endothelia and subendothelia of the human umbilical cord using a tedious procedure. We established a simple method to isolate abundant MSCs from human umbilical cord tissues (UC). 36 full-term umbilical cords were obtained. MSCs were isolated after enzyme digestion of minced cord fragments. The mean nucleated cells isolated from UC was 1.13±0.37×106/cm UC. A total of 1×10e10 MSCs was obtained after several passages over 4 weeks. CFU-F frequency is 1:1609. The population doubling time was approximately 28.02±10.53 h in passage 2 cells. The MSC cells were positive for CD13, CD29, CD44, SH-2, SH-3, CD166 and HLA class I (A, B, C), but were negative for CD34, CD38, CD45, CD31 and HLA-DR. More than 80% cells were in G0-G1 phase, whereas a small population of cells was engaged in proliferation (S+G2+M=9.16%). Under specified culture conditions, the MSC cells differentiated into adipocytes, osteoblasts and neural cells. The MSCs were also found to express cytokines of SCF, LIF, M-CSF, Flt3-ligand, IL-6, GM-CSF, G-CSF, VEGF, and SDF-1. When co-cultured with CD34+ cells from UC blood, the UC-derived MSCs were able to support the hematopoiesis of long-term culture-initiating cells. These findings suggested that abundant MSCs can be isolated simply and effectively from the whole cord tissue. Umbilical cords may be an attractive source of MSCs for tissue engineering, cord blood expansion and cord blood transplantation.

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Umbilical Cord Blood Transplantation: A New Alternative Option

Hematology ◽

10.1182/asheducation-2005.1.377 ◽

2005 ◽

Vol 2005 (1) ◽

pp. 377-383 ◽

Cited By ~ 61

Author(s):

William Tse ◽

Mary J. Laughlin

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cord Blood ◽

Hematopoietic Stem Cell ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Ex Vivo ◽

Cord Blood Transplantation ◽

Alternative Source ◽

Hematopoietic Stem

Abstract Allogeneic hematopoietic stem cell transplantation is a life-saving procedure for hematopoietic malignancies, marrow failure syndromes, and hereditary immunodeficiency disorders. However, wide application of this procedure is limited by availability of suitably HLA-matched adult donors. Umbilical cord blood (UCB) has being increasingly used as an alternative hematopoietic stem cell source for these patients. To date, over 6000 UCB transplant procedures in children and adults have been performed worldwide using UCB donors. Broader use of UCB for adult patients is however limited by the available infused cell dose. This has prompted intensive research on ex vivo expansion of UCB stem cells and UCB graft-engineering including accessory cells able to improve UCB engraftment and reconstitution and for tissue regenerative potential. Recently, two large European and North American retrospective studies demonstrated that UCB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack HLA-matched adult donors. UCB is anticipated to address needs in both transplantation and regenerative medicine fields. It has advantages of easy procurement, no risk to donors, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite HLA disparity.

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