26 7 17

................................................................ - 1 -

I.

................................................................... - 1 -

II.

......................................................................... - 2 -

III. ......................................................................... - 2 IV.

......................................................................... - 3 -

V.

......................................................................... - 3 -

1.

.................................... - 3 -

2.

.................................... - 3 -

3.

...................................... - 4 -

4.

.................................... - 4 -

5.

.............................. - 5 -

6.

................................................ - 5 -

7.

........................................................ - 5 -

(1)

Tissue ................................................................. - 5 -

(2)

.................................................. - 6 -

(3)

.................................................................... - 6 -

(4)

.................................................................... - 6 -

(5)

............................................ - 6 -

(6)

.............. - 6 -

(7)

.............................................................. - 6 -

(8)

.................................................... - 7 -

.......................................................... - 8 -

I.

....................................................................... - 8 -

II.

....................................... - 10 -

1.

............................................................. - 10 -

(1)

..................... - 10 -

(2)

................................................... - 21 -

(3)

............................................... - 22 -

(4)

Tissue ..................................... - 24 -

(5)

................................................. - 28 -

(6)

......................................................... - 28 -

2.

....................................................... - 29 -

(1)

............................... - 29 -

(2)

Tissue ....... - 32 -

(3)

......... - 34 -

(4)

......................................... - 45 -

III. - 47 1.

........................................... - 47 -

2.

....................................................... - 47 -

(1)

23 1 ........................................ - 47 -

(2)

23 1 .............. - 47 -

(3)

(1)
............................... - 48 -

(4)

(2)
.... - 50 -

3.
IV.

.......................................................................... - 55 ................................... - 56 -

1.

................................. - 56 -

(1)

....................................................... - 56 -

(2)

................................................................. - 56 -

2.

..................................................... - 56 -

3.

................................................. - 57 -

(1)

..................................................... - 57 -

(2)

......................... - 62 -

4.
V.

.......................................................................... - 63 ....................... - 64 -

1.

......................... - 64 -

(1)

........................................................... - 64 -

(2)

............................................................... - 64 -

(3)

............................................................... - 64 -

2.

..................................................... - 66 -

(1)

....................................................... - 66 -

(2)

....................................................... - 66 -

(3)

......................................... - 66 -

(4)

........................................... - 68 -

3.
(1)

..................................................... - 69 -

(2)

..................................................... - 71 -

(3)

......................................... - 73 -

(4)

................................... - 74 -

(5)

......... - 74 -

4.

VI.

........................... - 69 -

.......................................................................... - 77 ............................................................................ - 78 -

1
I.

26 2

First Author Nature STAP1

2 2Nature

First Author
Tissue Engineering Part A3Tissue
4

Tissue Tissue

26 2 21 26 3 15

26 3 15 A
1
2

Stimulus-triggered acquisition of pluripotency

Stimulus-triggered fate conversion of somatic cells into pluripotency
26
Bidirectional developmental potential in reprogrammed cells with acquired pluripotency
26
Mary Ann Liebert, Inc.,

Tissue Engineering
1
24 4.065

(accept)

2 4 Haruko Obokata, et.al, The Potential of

Stem Cells in Adult Tissues Representative of the Three Germ Layers (TISSUE ENGINEERING: Part
A, Volume 17, Numbers 5 and 6) 23 )
Isolation of pluripotent adult stem cells discovered from tissues derived from all
three germ layers
23

- 1 -


26 3 17

26 3 28

31

26 3 31 .

II.

III.

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26 3 31 7 16

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Nature Tissue

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CDB

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6.

National Institutes of HealthNIH

W

X Zen-Bio, Inc.Zen-Bio

Harlan

7.

(1)

Tissue
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Tissue
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(3)

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(6)

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- 6 -

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I.

V.

20
41

91

21
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Tissue Tissue
First Author
S R Q 1
Corresponding AuthorT

9 30

Tissue Tissue

11 11

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23
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25
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Nature Nature

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Nature Nature

26
2

Nature

3 31

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II.

1.

(1)

8910

a.

1 1 1.1 1.5 6

(a)

i.

11

10

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45 5 6 48 21

2 1 15

2 1 1

NIH
NIH
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iii.

12

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NIH

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i.

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12
13

105 NIH
2
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425

32 1

35

35

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4500
1 80 20 80

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25 Fig. 1

(a)

i.

ii.

14

iii.

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W W

v.

32

W 21

(b)

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i.

14

C-kit positive stem cells

- 12 -


ii.

c.

26 Fig. 2
1
1
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i.

ii.

1
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1516

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1
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15

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14 6 28 55 4 837

1
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21

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32

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i.

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71 Fig. 15 2

2
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2 2

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iv.

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73 Fig. 17 3

3
(a)

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3
3
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46 2 2.6 References 24 31 58
3 3.6 References76 4 4.6 References
1 49 93 5 5.6 References

(a)

i.

17

17

12 1

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ii.

iii.

iv.

v.

32

21
3 5

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i.

ii.

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3 5

53 Fig. 1018

g.

(a)
i.

Muscle

(i)

1 1
1 1

(ii)

1
1

(iii) 1

1
(iv)

Zen-Bio
1 Zen-Bio
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19

(v)

18

19

32

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1

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Zen-Bio 1
21
ii.

hepatocyte

(i)

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2
2

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2

(iv)

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2

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32

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21
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in vitro
6

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86 Fig. 20
(
(a)

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21

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ii.

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Harlan Harlan

v.

32

Harlan 21

(b)

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i.

ii.

(2)

a.

42 Fig. 7(

2 Oct4/DAPI

SSEA-1/DAPIFigure 7 Pluripotent marker

expressions/Spheres at day 5 expressed pluripotent cell markers Oct4 and
SSEA-1. 2

- 21 -


22
b.

57 Fig. 14 3

3
Figure 14 Teratoma like mass from

bone marrow spheres contained nerve expressing betaIII-tubuline

(left)(ectoderm), muscle expressing desmin (middle)(mesoderm) and duct like
structure expressing AFP (right)(endoderm).

(3)

a.

28 2 2.2.1 11 B. Optimistic pressure

13 destroy mature cells.

A. Cell sorter

B. Optimistic pressureC. Trituration

using thin-glass pipette

B. Optimistic
pressure

B. Optimistic pressure
Optimistic pressure

2324
b.

30 2 2.3.2 only small

cells.

22

23

24

Fig. 7 Fig. 6 G Fig. 7 Fig. 8

Oct4 Fig. 7

optimistic pressure

osmotic pressure

Optimistic pressureOsmotic pressure

B. Osmotic pressure

2
2.2.1

- 22 -

Fig. 3

c.

33 2 2.3.6 three germ

layers was examined.

Fig. 8

25
d.

36 2 2.5 The mechanisms or process to

express pluripotent cell markers in spheres may be distinct from ES
cells or iPS cells.

iPS

iPS

e.

68 4 4.3.3 3 Neural cells (ectoderm

lineage) 13 CK18 (Fig. 17x - A,B,C) was seen.

in vitro

Fig. 17i
- A,B,C Fig. 17
Fig. 17

25

1 4 4.3.2 66 2

- 23 -

(4)

Tissue

a.

54 Fig. 11 3

(a)

3 3.3.1 4 6 The addition

of 14 into endodermal tissue.
Tissue
611 11 3 The addition of 11
into endodermal tissue.
Fig. 4

(b)

Tissue
Ectoderm Tissue 26

Tissue

(c)

Mesoderm Tissue 27

Tissue

(d)

Endoderm Tissue 28

Tissue

Tissue
Tissue
Tissue

b.

73 Fig. 17 27

26
27
28

Fig. 4 B
Fig. 4 E
Fig. 4 H

- 24 -

(a)

4 4.3.3

Tissue
611 14 Spinal spheres, myospheres, 612 4
procured from BM.
Fig. 5

(b)

Tissue
spinal cord Tissue 29

Tissue

(c)

muscle Tissue 30

Tissue

(d)

lung Tissue 31

Tissue

(e)

Tissue Fig. 5

32 Tissue Fig. 5

Tissue
Tissue
Tissue

c.

68 4 4.3.4 6 4
Tissue generated
from spinalspheres 10 1 duct like tissue (endoderm)

29
30
31
32

Fig. 5 A
Fig. 5 C
Fig. 5 B
Tissue Fig.4
Map2
MyoD

- 25 -

(Fig. 18).

(a)

Fig. 18
Tissue 613 4 2 Tissue generated from
spinal spheres
9 5 duct-like tissue (endoderm; Fig.
6Cv, Cvi).
Fig. 6 Ai B Aii C

(b)

Tissue
Tissue Fig. 6 Ai
B Aii 14
Fig. 18
7

Tissue
Tissue
Tissue

d.

74 Fig. 18

(a)

4 4.3.4 6 4 Tissue
generated from spinalspheres
8 2
duct like cuboidal
epithelium (endoderm) (Fig.18).
8 3 Tissue
generated from myospheres 10 1 duct like tissue
(endoderm) (Fig. 18).

Tissue 613 4 2
Tissue generated from spinal spheres 6 6
duct-like tissue (endoderm; Fig. 6Bv, Bvi).
6 7
Tissue generated from myospheres 9 5 duct-like
- 26 -

tissue (endoderm; Fig. 6Cv, Cvi).

Fig. 6 Ai
B Aii C
(b)

Tissue
Tissue
Tissue

Tissue
Tissue
Tissue

e.

75 Fig. 19

(a)

4 4.3.4 10 2 Tissue
generated from pneumospheres 11 7 cartilage
(mesoderm) (Fig.19), gland (ectoderm) (Fig.19).

Tissue 613 9 6 Tissue generated from

pneumospheres 1 3 cartilage (mesoderm; Fig.
6Diii, Div), and gland (ectoderm; Fig. 6Dv, Dvi).

Fig. 6 Aiii D

(b)

Tissue
Tissue
Tissue

Tissue
Tissue
Tissue

- 27 -

33

(5)
a.

29 2 2.2.1 14 C. Trituration using

thin-glass pipette 17 by mechanical stress.

A. Cell sorter

B. Optimistic pressureC. Trituration

using thin-glass pipette
C. Trituration
using thin-glass pipette

pipetting

b.

81 5

5
34
c.

Curriculum Vitae Patent

"Patent""Haruko
Obokata, Charles A. Vacanti. Sub Population of Retained Embryonic Like Cells"

(6)

33
34

5 CDB

- 28 -

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35

(1)

2 5

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41
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38
39
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41

5 5.2.1 5.3.1
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CDB U

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22 8 9
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Fig. 26

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43
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first author
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Nature

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optimistic pressure

optimistic pressureosmotic
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optimistic
pressureosmotic pressure

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49

(a)

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