Germ plasm-like Dot cells maintain their wound regenerative function after in vitro expansion.
1. Wounds in fetal skin heal without scarring; however, the mechanism for this is unknown. We have identified a novel group of protein and nucleotides-positive particles in fetal and adult mouse blood and in human blood, and termed them 'Dot cells'. Freshly isolated Dot cells regenerate wounds with less scarring and can be cultured without feeder layers. 2. Because the morphology of Dot cells has never been described, in the present study we describe the specific characterizations of Dot cells, including their growth pattern in vitro, and their expressions of stem cell markers using fluorescent cell sorting analyses and immunofluorescent histology. Our data indicates that cultured Dot cells express stem cell surface markers and embryonic stem cell transcription markers, such as Oct4, Nanog and Sox-2. In addition, Dot cells express VASA, the germ plasm specific marker. 3. To confirm whether Dot cells maintain their wound regenerative activity after in vitro expansion, in vitro cultured Dot cells were transplanted to wounded mice. Dot cells from albino mice maintain their wound regenerative activities after intravenous transplantation to black-background diabetic mice. In addition, Dot cells regenerate both the epithelial and dermal cells in the wounds of wild-type mice. The regenerated hair follicles, smooth muscle and dermal tissues express transiently to VASA. 4. Our data demonstrate that Dot cells are newly identified organisms located in the blood and bone marrow of mammals. They express germ cell, embryonic stem cell and adult stem cell markers. Dot cells maintain their regenerative function after in vitro expansion.
Kong
Wuyi
W
Hagey laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA. wkong@stanford.edu
Li
Shaowei
S
Lorenz
H Peter
HP
D053687:Adult Stem Cells / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D036102:Peripheral Blood Stem Cell Transplantation; D012038:Regeneration / Q000502:physiology*; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D012879:Skin Physiological Phenomena; D018874:Spheroids, Cellular / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
D000954:Antigens, Surface
Mech Dev. 1998 Jul;75(1-2):81-93
9739112
J Mol Cell Cardiol. 2007 Apr;42(4):746-59
17300799
Nature. 2004 Apr 8;428(6983):668-73
15034594
Nature. 2002 Jul 4;418(6893):41-9
12077603
Development. 1990 Jun;109(2):425-33
2119289
Leukemia. 2006 May;20(5):857-69
16498386
Nat Med. 2002 Apr;8(4):403-9
11927948
Science. 2002 Sep 27;297(5590):2256-9
12215650
Hum Reprod. 2009 Jun;24(6):1359-72
19251728
Nature. 2008 Nov 27;456(7221):502-6
18806774
Cell. 2007 Nov 30;131(5):861-72
18035408
Gene Ther. 2002 May;9(10):606-12
12032706
Nat Med. 2000 Nov;6(11):1229-34
11062533
J Cell Sci. 2004 Jun 15;117(Pt 14):2971-81
15173316
Leuk Res. 2008 Feb;32(2):211-3
17675154
Science. 2007 Feb 9;315(5813):760-1
17289957
Blood. 2005 Sep 15;106(6):1901-10
15890683
Int Rev Cytol. 1975;43:229-80
770367
Annu Rev Med. 2005;56:509-38
15660525
Stem Cells. 2006 Jun;24(6):1594-604
16556707
Science. 2000 Dec 1;290(5497):1779-82
11099419
Science. 1998 Mar 6;279(5356):1528-30
9488650
Int J Dev Biol. 1994 Jun;38(2):193-9
7526880
Dev Biol. 2002 Dec 1;252(1):100-18
12453463
Leukemia. 2007 Feb;21(2):297-303
17136117
Development. 1998 May;125(9):1569-78
9521895
Science. 1992 Mar 6;255(5049):1216-7
1372132
Blood. 1998 Jun 15;91(12):4523-30
9616148
Dev Dyn. 2005 Mar;232(3):593-608
15704150
Science. 2007 Dec 21;318(5858):1917-20
18029452
Am Sci. 1976 May-Jun;64(3):279-90
776052
Exp Cell Res. 2008 Apr 15;314(7):1529-39
18295204