Okayama nakanishi 114.002

2. Candidate cell sources for regenerative medicine include:
1. ES cells, 2. Fetal cells, and 3. Adult stem cells.

3. Umezawa, A., et al.. Mol. Cell. Biol. 11: 920-927, 1991
Marrow stroma serves a microenvironment or niche
for hematopoietic cells

4. Fat Neuron
Bone
Cartilage
Cardiomyocyte
Skeletal myocyte
DefaultDefault With exposure to inducesWith exposure to induces
Differentiated phenotypes of marrow stromal cells

5. ねずみ５匹ねずみ５匹
エックス線写真エックス線写真
4 weeks
2 weeks
In vivoIn vivo osteogenic activity in marrow stromal cellsosteogenic activity in marrow stromal cells

6. The injected cells generated bone

7. Generation of a delayed union modelGeneration of a delayed union model
A 5-mm section of syngeneic mouse femur at the diaphysis was removed.A 5-mm section of syngeneic mouse femur at the diaphysis was removed.
Bone was not formed without any treatment
Marrow stromal cells as a source of cell therapy
４週4 weeks
The generated bones were transplanted into
the femur bone defects.

8. PLGA sheets
CollagenCollagen
microspongemicrosponge
overlay the interstices ofoverlay the interstices of
the fabricated web-likethe fabricated web-like
Generation of bone tissue of desired sizes and shapes
Sheet-style biodegradable polymer,
PLGA (200 um thick,) as a scaffold
Hybridization of the PLGA
with collagen microsponge

9. 4.3 mm
KUSA cells on
PLGA/COL
Laminating mesh sheets on bone defect

10. 4W
8W
40x 100x
Cell transplantation with PLGA/COL mesh

11. Strategy for Bone Tissue Engineering
Implantation to bone defect site
adapted to various shape
growth factor hybrid
PLGA/collagen mesh cell seeding
apatite hybrid
laminate
curl
roll

12. The cell-seeded sheets were rolled up
around a silicone rod,and cultivated in
vivo for 4 weeks at the subcutaneous
tissue.
Cylinder-shaped bone

13. Bone knots
bone of more complex shapes
We can control bone shape completely

14. Mimic shaping of phalanges
from -TCP blockβ
Transplantation
Osteoblast seeded mesh
Cover the β-TCP core
with meshChondrocyte seeded mesh
Strategy for bone tissue engineering

15. Generation of phalanges by the PLGA hybrid sheet
with marrow-derived mesenchymal cells.
phelage-like bone
Thumb of
the graduate student

16. 2W 4W
8W
Implantation of MSC-x
Pellet into the
subcutaneous tissue of
immunodeficient mice
Enchondral
Ossification

17. Implantation of MSC-x pelleted micromasses in the nude mic
2W 4W 8W
Toluidine blue stain
HE
Enchondral
Ossification

18. 2W 4W 8W
Toluidine blue stain
HE
Implantation of MSC-x pelleted micromasses in the nude mic
Enchondral
Ossification

19. Selection by chondrocyte- and osteoblast-
specific cis-regulatory element
pCS2-Venus
p742-Venus
UE7T-9 UE7T-13
UE6E7T-12 UBE6T-6
OSE cis-regulatory activity
Chondrocyte-specific
cis-regulatory element
of the Col alpha2(XI)
gene
Relativeluciferaseactivity
Cells

20. Stem cells
Selection by
surface antigens
and cis-elements
ProgenitorsTargeting
of differentiation

21. Keio University
School of Medicine
Dept of Medicine
Makino, Shinji
Fukuda, Keiichi
Kizaki, Masahiro
Dept of Physiology
Okano, Hideyuki
Shimazaki, Takuya
Kohyama, Jun
Saitama Medical College
Gojo, Satoshi
Kyo, Shunei
Dept of Orthopedics
Toyama, Yoshiaki
Imabayashi, Hideaki
Kensuke, Ochi
Dept of Microbiology
Segawa, Kaoru
NIH, USA
Ko, Minoru SH
Kumamoto University
Taga, Tetsuya
Nakashima, Kinichi
National Cancer Center, Jpn
Kiyono, Tohru
Helix Institute
Isogai, Takao
Sugiyama, Tomoyasu
Irie, Ryotaro

22. Takeda
Mori Tsuchiya
Matsumoto

23. National Center for Child Health and Development

24. ほねほね
あしばあしば
0.3%0.3% コラーゲン ゲル・ 含有コラーゲン ゲル・ 含有
ポリ乳酸スポンジポリ乳酸スポンジ
肉眼所見肉眼所見 電子顕微鏡電子顕微鏡