Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture.
BACKGROUND
Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated.


METHODS
Umbilical cord-derived MSCs (UC-MSCs) were cultured from the Wharton's jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay.


RESULTS
Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays.


CONCLUSIONS
These data suggest the potential therapeutic application of Wharton's jelly-derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.
Bakhshi
Tiki
T
Division of Maternal-Fetal Medicine, The University of Texas Medical School at Houston, Houston, Texas, USA.
Zabriskie
Ryan C
RC
Bodie
Shamanique
S
Kidd
Shannon
S
Ramin
Susan
S
Paganessi
Laura A
LA
Gregory
Stephanie A
SA
Fung
Henry C
HC
Christopherson
Kent W
KW
D002469:Cell Separation / Q000379:methods*; D048430:Cell Shape; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D013997:Time Factors
J Virol. 2002 Jul;76(13):6636-42
12050376
Bone Marrow Transplant. 2006 Feb;37(4):359-66
16400333
Stem Cells. 2005 Feb;23(2):220-9
15671145
Stem Cells. 2003;21(1):50-60
12529551
J Immunol. 2002 Dec 15;169(12):7000-8
12471135
Braz J Med Biol Res. 2003 Sep;36(9):1179-83
12937783
Cytotherapy. 2006;8(4):315-7
16923606
Br J Haematol. 2003 Apr;121(2):368-74
12694261
Stem Cells. 2006 Mar;24(3):781-92
16223852
Stem Cells. 2004;22(7):1330-7
15579650
N Engl J Med. 1989 Oct 26;321(17):1174-8
2571931
Blood Cells. 1994;20(2-3):560-4; discussion 564-5
7749121
Stem Cells. 2004;22(5):649-58
15342929
Biochem Soc Trans. 1991 Feb;19(1):29S
1709890
Biol Blood Marrow Transplant. 2007 Dec;13(12):1477-86
18022578
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4698-703
9114054
Methods Mol Med. 2002;63:123-41
21437804
Blood Cells. 1994;20(2-3):227-33; discussion 233-4
7749099
Blood. 1998 Jan 1;91(1):111-7
9414274
Int J Mol Med. 2006 Dec;18(6):1089-96
17089012
Chin Med J (Engl). 2005 Dec 5;118(23):1987-93
16336835
Proc Natl Acad Sci U S A. 1989 May;86(10):3828-32
2566997
Exp Hematol. 2002 Aug;30(8):870-8
12160838
Proc Natl Acad Sci U S A. 1990 May;87(9):3584-8
2333304
Stem Cells. 2003;21(1):105-10
12529557
Cytotherapy. 2004;6(4):311-7
16146883