Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice

Jee Hyun An; Hyojung Park; Jung Ah Song; Kyung Ho Ki; Jae Yeon Yang; Hyung Jin Choi; Sun Wook Cho; Sang Wan Kim; Seong Yeon Kim; Jeong Joon Yoo; Wook Young Baek; Jung Eun Kim; Soo Jin Choi; Wonil Oh; Chan Soo Shin

doi:10.1089/ten.tea.2012.0047

Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice

Jee Hyun An
, Hyojung Park
, Jung Ah Song
, Kyung Ho Ki
, Jae Yeon Yang
, Hyung Jin Choi
, Sun Wook Cho
, Sang Wan Kim
, Seong Yeon Kim
, Jeong Joon Yoo
, Wook Young Baek
, Jung Eun Kim
, Soo Jin Choi
, Wonil Oh
, Chan Soo Shin

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

Original language	English
Pages (from-to)	685-696
Number of pages	12
Journal	Tissue Engineering - Part A
Volume	19
Issue number	5-6
DOIs	https://doi.org/10.1089/ten.tea.2012.0047
State	Published - 1 Mar 2013

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An, J. H., Park, H., Song, J. A., Ki, K. H., Yang, J. Y., Choi, H. J., Cho, S. W., Kim, S. W., Kim, S. Y., Yoo, J. J., Baek, W. Y., Kim, J. E., Choi, S. J., Oh, W., & Shin, C. S. (2013). Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice. Tissue Engineering - Part A, 19(5-6), 685-696. https://doi.org/10.1089/ten.tea.2012.0047

@article{2bc2442b1f1e475197b0fc0110a228c5,

title = "Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice",

abstract = "Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.",

author = "An, \{Jee Hyun\} and Hyojung Park and Song, \{Jung Ah\} and Ki, \{Kyung Ho\} and Yang, \{Jae Yeon\} and Choi, \{Hyung Jin\} and Cho, \{Sun Wook\} and Kim, \{Sang Wan\} and Kim, \{Seong Yeon\} and Yoo, \{Jeong Joon\} and Baek, \{Wook Young\} and Kim, \{Jung Eun\} and Choi, \{Soo Jin\} and Wonil Oh and Shin, \{Chan Soo\}",

year = "2013",

month = mar,

day = "1",

doi = "10.1089/ten.tea.2012.0047",

language = "English",

volume = "19",

pages = "685--696",

journal = "Tissue Engineering - Part A",

issn = "1937-3341",

publisher = "Mary Ann Liebert Inc.",

number = "5-6",

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An, JH, Park, H, Song, JA, Ki, KH, Yang, JY, Choi, HJ, Cho, SW, Kim, SW, Kim, SY, Yoo, JJ, Baek, WY, Kim, JE, Choi, SJ, Oh, W & Shin, CS 2013, 'Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice', Tissue Engineering - Part A, vol. 19, no. 5-6, pp. 685-696. https://doi.org/10.1089/ten.tea.2012.0047

TY - JOUR

T1 - Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice

AU - An, Jee Hyun

AU - Park, Hyojung

AU - Song, Jung Ah

AU - Ki, Kyung Ho

AU - Yang, Jae Yeon

AU - Choi, Hyung Jin

AU - Cho, Sun Wook

AU - Kim, Sang Wan

AU - Kim, Seong Yeon

AU - Yoo, Jeong Joon

AU - Baek, Wook Young

AU - Kim, Jung Eun

AU - Choi, Soo Jin

AU - Oh, Wonil

AU - Shin, Chan Soo

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

AB - Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

UR - https://www.scopus.com/pages/publications/84873401330

U2 - 10.1089/ten.tea.2012.0047

DO - 10.1089/ten.tea.2012.0047

M3 - Article

C2 - 23215868

AN - SCOPUS:84873401330

SN - 1937-3341

VL - 19

SP - 685

EP - 696

JO - Tissue Engineering - Part A

JF - Tissue Engineering - Part A

IS - 5-6

ER -

Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice

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