Primitive stromal cells can be isolated from umbilical cord Wharton's jelly (UC-PSCs). Umbilical cord can be easily obtained without causing pain to donors, and the procedure avoids ethical and technical issues. UC-PSCs are more primitive than mesenchymal stem cells (MSCs) isolated from some other tissue sources. In this study, UC-PSCs were induced to differentiate into insulin-producing cells, and compared with bone marrow–derived MSCs (BM-MSCs) for their pancreatic differentiation potential. UC-PSCs showed significantly higher proliferation than BM-MSCs. During pancreatic induction, UC-PSCs formed larger islet-like cell clusters than BM-MSCs. Immunocytochemical analysis showed that higher expression of the pancreatic-specific transcription factor PDX-1 was detected in differentiated UC-PSCs than in differentiated BM-MSCs. Flow cytometry analysis demonstrated that the percentage of differentiated UC-PSCs expressing pancreatic-specific marker C-peptide was 72% higher than differentiated BM-MSCs. Radioimmunoassay revealed that differentiated UC-PSCs secreted significantly more insulin than differentiated BM-MSCs. These results demonstrated that UC-PSCs had higher pancreatic differentiation potential than BM-MSCs. Therefore, UC-PSCs are more suitable for pancreatic tissue engineering in the treatment of type I diabetes than BM-MSCs.
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References
1.
VantyghemM.C., Marcelli-TourvielleS., PattouF., NoelC.Effects of non-steroid immunosuppressive drugs on insulin secretion in transplantation. Ann Endocrinol, 68:21. 2007.
2.
WilliamsM.E., LacsonE.Jr., TengM., OfsthunN., LazarusJ.M.Hemodialyzed type I and type II diabetic patients in the US: characteristics, glycemic control, and survival. Kidney Int, 70:1503. 2006.
3.
ShapiroA.M.J., LakeyJ.R.T., RyanE.A., KorbuttG.S., TothE., WarnockG.L., KnetemanN.M., RajotteR.V.Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med, 343:230. 2000.
4.
ShapiroA.M., RicordiC.Unravelling the secrets of single donor success in islet transplantation. Am J Transplant, 4:295. 2004.
5.
LumelskyN., BlondelO., LaengP., VelascoI., RavinR., McKayR.Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science, 292:1389. 2001.
6.
SegevH., FishmanB., ZiskindA., ShulmanM., Itskovitz-EldorJ.Differentiation of human embryonic stem cells into insulin producing clusters. Stem Cells, 22:265. 2004.
7.
ZulewskiH., AbrahamE.J., GerlachM.J., DanielP.B., MoritzW., MüllerB., VallejoM., ThomasM.K., HabenerJ.F.Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes, 50:521. 2001.
8.
AbrahamE.J., LeechC.A., LinJ.C., ZulewskiH., HabenerJ.F.Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin producing cells. Endocrinology, 143:3152. 2002.
9.
ZalzmanM., GuptaS., GiriR.K., BerkovichI., SappalB.S., KarnieliO., ZernM.A., FleischerN., EfratS.Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci, 100:7253. 2003.
HoriY., GuX., XieX., KimS.K.Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med, 2:347. 2005.
12.
KodamaS., KuhtreiberW., FujimuraS., DaleE.A., FaustmanD.L.Islet regeneration during the reversal of auto immune diabetes in NOD mice. Science, 302:1223. 2003.
13.
GoodwinH.S., BickneseA.R., ChienS.N., BoguckiB.D., QuinnC.O., WallD.A.Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers. Biol Blood Marrow Transplant, 7:581. 2001.
14.
SeoM.J., SuhS.Y., BaeY.C., JungJ.S.Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun, 328:258. 2005.
15.
StremB.M., ZhuM., AlfonsoZ., DanielsE.J., SchreiberR., BeyguiR., MacLellanW.R., HedrickM.H., FraserJ.K.Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury. Cytotherapy, 7:282. 2005.
16.
KernS., EichlerH., StoeveJ., KluterH., BiebackK.Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 24:1294. 2006.
17.
BakshD., YaoR., TuanR.Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells, 25:1384. 2007.
18.
In't AnkerP.S., NoortW.A., ScherjonS.A., Kleijburg-van der KeurC., KruisselbrinkA.B., van BezooijenR.L., BeekhuizenW., WillemzeR., KanhaiH.H., FibbeW.E.Mesenchymal stem cells in human second trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica, 88:845. 2003.
19.
LeeO.K., KuoT.K., ChenW.M., LeeK.D., HsiehS.L., ChenT.H.Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood, 103:1669. 2004.
20.
ZukP.A., ZhuM., AshjianP., De UgarteD.A., HuangJ.I., MizunoH., AlfonsoZ.C., FraserJ.K., BenhaimP., HedrickM.H.Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell, 13:4279. 2002.
21.
BarryF.P., MurphyJ.M.Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol, 36:568. 2004.
22.
HuY., LiaoL., WangQ., MaL., MaG., JiangX., ZhaoR.C.Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med, 141:342. 2003.
23.
TangD.Q., CaoL.Z., BurkhardtB.R., XiaC.Q., LitherlandS.A., AtkinsonM.A., YangL.J.In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes, 53:1721. 2004.
24.
OhS.H., MuzzonigroT.M., BaeS.H., LaPlanteJ.M., HatchH.M., PetersenB.E.Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest, 84:607. 2004.
25.
StenderupK., JustesenJ., ClausenC., KassemM.Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone, 33:919. 2003.
26.
NishidaS., EndoN., YamagiwaH., TanizawaT., TakahashiH.E.Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. J Bone Miner Metab, 17:171. 1999.
27.
MuellerS.M., GlowackiJ.Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. J Cell Biochem, 82:583. 2001.
28.
ZhangH., FazelS., TianH., MickleD.A., WeiselR.D., FujiiT., LiR.K.Increasing donor age adversely impacts beneficial effects of bone marrow but not smooth muscle myocardial cell therapy. Am J Physiol Heart Circ Physiol, 289:H2089. 2005.
29.
MedicettyS., BledsoeA.R., FahrenholtzC.B., TroyerD., WeissM.L.Transplantation of pig stem cells into rat brain: proliferation during the first 8 weeks. Exp Neurol, 190:32. 2004.
30.
FuY.S., ChengY.C., LinM.Y.A., ChengH., ChuP.M., ChouS.C., ShihY.H., KoM.H., SungM.S.Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for parkinsonism. Stem Cells, 24:115. 2006.
31.
YangC.C., ShihY.H., KoM.H., HsuS.Y., ChengH., FuY.S.Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. PLoS ONE, 3:e3336. 2008.
32.
LuL.L., LiuY.J., YangS.G., ZhaoQ.J., WangX., GongW., HanZ.B., XuZ.S., LuY.X., LiuD., ChenZ.Z., HanZ.C.Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica, 91:1017. 2006.
33.
CanA., KarahuseyinogluS.Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells, 25:2886. 2007.
34.
SarugaserR., LickorishD., BakshD., HosseiniM.M., DaviesJ.E.Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells, 23:220. 2005.
35.
WuK.H., ZhouB., LuS.H., FengB., YangS.G., DuW.T., GuD.S., HanZ.C., LiuY.L.In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells. J Cell Biochem, 100:608. 2007.
36.
WeissM.L., MedicettyS., BledsoeA.R., RachakatlaR.S., ChoiM., MerchavS., LuoY., RaoM.S., VelagaletiG., TroyerD.Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells, 24:781. 2006.
37.
WangH.S., HungS.C., PengS.T., HuangC.C., WeiH.M., GuoY.J., FuY.S., LaiM.C., ChenC.C.Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells, 22:1330. 2004.
38.
TimperK., SeboekD., EberhardtM., LinscheidP., Christ-CrainM., KellerU., MüllerB., ZulewskiH.Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagons expressing cells. Biochem Biophys Res Commun, 341:1135. 2006.
