Darwin%20J.%20Prockop,%20M.D.,%20Ph.D., - PowerPoint PPT Presentation

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Darwin%20J.%20Prockop,%20M.D.,%20Ph.D.,

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Title: Darwin%20J.%20Prockop,%20M.D.,%20Ph.D.,


1
??/????????????????????????
  • Darwin J. Prockop, M.D., Ph.D.,
  • Director, Center for Gene Therapy, Tulane
    University Health Sciences Center, New Orleans,
    LA
  • ???violet39 (DXY)

2
?????????????
  • Cohnheim (1867) ?????????????????????????
  • ?????????????????????????????????????????????????
    ???

3
??????????????
  • ????????????
  • ?????????????????????
  • ????????????????????
  • ???????????????????????

4
??/??????
  • ??????????????????????????????????
  • ??????????????

5
??????????????????
????,????
???????
???????
????????
6
??
  • 1??????????????????
  • 2????,???????
  • 3????,??????????????

7
??
  • 1??????????????????
  • ???????????????
  • a????????????
  • b?????
  • c??????????????
  • (?? Prockop et al. PNAS 100(1) 11917-23, 2003)

8
  • 2??????????
  • ?????(CD34 ? CD133)?
  • ?????
  • ?????????
  • ???????? (MSCs)?
  • ????????????

9
?????????????
  • ??
  • ???????????
  • ?????????
  • ??????,???????HSCs????
  • ?????,?????????????
  • ????,???????MSCs

10
  • Friedenstein,1976,??????(MSCs)??????
  • ?????????110,000?100,000
  • ?????
  • ???????????????????????

11
????,????????????
/- ?? /- ??????
?????
????
????
????
12
???MSCs????
  • 1?????
  • ?????,
  • ????????
  • 2??????????
  • 3???????
  • 4?????????????????

13
MSCs???
  • ?2ml??????
  • ???5????? MSCs
  • ??2????

14
??????
??12??,????????2000?? (Colter, DiGirolamo,
Prockop, 2000)
15
???? 1?????? 2???????? 3???,??,????????(RS
??)?
16
?????????????????
17
??????
????? ????? ????????????? ?? ?????????????
18
???????
?1
11111111111
cm2????
MSC????35S???????,???????35S???????(C)???????(M)??
??????????,???????
19
????????????
??????35kDa???
?????
??
?????35S????????????????(F)??????(L)???????()????
??????????????????????
20
??????16??,SELDI TOF
Dickkopf-1, Wnt ?????????? ???35kDa?????????????
?????????Wnt??????????????????????????
21
??Dkk-1??MSCs?????????(????)
?????????????
?????????????
????
????
22
Dkk-1???????
????
?
23
Wnt???,Dkk-1??????hMSCs?????
Dkk-1Wnt??????????
????,??,??
24
MSCs?????????????
  • a????????????????,??????Wnt?????????Dkk-1?
  • b??Dkk-1?????,????Wnt???????????Wnt-5a?,???????
  • c?????????,?????????,???4-6?,???????????

25
??????(4 - 6Xs)
??/??
26
Dickkopf-1(Dkk-1)
  • Wnt??????????
  • ?????????Wnt????,???????
  • ???????MSCs??
  • ??????Dkk-1?????????MSC?????????

27
????????MSCs??
RS???? ???? ???
RS?? ????,????
MSC ????
???? (???,???, ???)
??????
????
????
????
????
?????
28
??MSCs???????????
  • 2ml?????2?????5???????
  • ???????
  • ??????,???????????
  • NIH??430?????tulane??,??????????????????

29
??
  • 1???????????????????
  • 2????,????????
  • 3????,???????????????

30
????SAEGFP/MSCs
???????(SAE) GFP /MSCs
( 20 )
( 40 )
?????????????????,GFP???MSCs??????????,???
?????????,???????
31
3. MSCs???????????Spees et al. PNAS 2003
?? ??????
??MSCs
??
????????
1??? 2?????(?)
3????? (Wnt 5a, VEGF, PDGF, BDNF, NT-3)
???MSCs?? (????)
32
?????????
  • ??????????
  • ????????
  • ?????????????????????

33
?????
  • ??????????????????????
  • ?????????????????????????

34
???????????
  • ???,3000?????????,???????????500,000???
  • ??????????
  • ???????????????????????
  • ????????MSCs?????????,??????????

35
????????
  • MSCs??
  • ????
  • ??????
  • ??????????????????
  • (Hoffstetter et al. PNAS 2002)

36
(No Transcript)
37
????????
  • ????????
  • 1?????MSCs??????
  • ???? ????
  • ??? 0/10 6.8 /- 0.4 SEM
  • ??? 7/12 9.2 /- 0.4 SEM

  • (p0.013)
  • 2????????

38
hMSCs????????
39
?????????
  • ?????????,???????
  • ???????????,???????????MSCs??????
  • ??????????
  • ??????????
  • (???????????????????????????)

40
??????????
  • Prockop, D.J., C.A. Gregory and J.L. Spees.
    One strategy for cell and gene therapy
    Harnessing the power of adult stem cells to
    repair tissues.
  • Proceedings of the National Academy of
    Sciences 100(1)11917-11923(2003).
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