140717 Committee Report

7/24/2019 140717 Committee Report

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1

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1. .................................... - 3 -

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

6. ................................................ - 5 -

7. ........................................................ - 5 -

(1)

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

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(3) .................................................................... - 6 -

(4) .................................................................... - 6 -

(5) ............................................ - 6 -

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2

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1. ............................................................. - 10 -

(1) ..................... - 10 -

(2) ................................................... - 21 -

(3) ............................................... - 22 -

(4)

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

(5) ................................................. - 28 -

(6) ......................................................... - 28 -

2. ....................................................... - 29 -

(1) ............................... - 29 -

(2)

Tissue ....... - 32 -

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

2.

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

(1) 23 1........................................ - 47 -

(2) 23 1.............. - 47 -

(3) (1)............................... - 48 -

(4) (2).... - 50 -

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1. ................................. - 56 -

(1)

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(2) ....................................................... - 66 -

(3) ......................................... - 66 -

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3. ........................... - 69 -

(1) ..................................................... - 69 -

(2) ..................................................... - 71 -

(3) ......................................... - 73 -

(4) ................................... - 74 -

(5) ......... - 74 -

4. .......................................................................... - 77 -

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- 1 -

1

.

26 2

First Author Nature STAP1

22Nature

First Author

Tissue EngineeringPart A3Tissue

4Tissue Tissue

5

26 2 21 26 3 15

26 3 15 A

1 Stimulus-triggered acquisition of pluripotency 2 Stimulus-triggered fate conversion of somatic cells into pluripotency 26

Bidirectional developmental potential in reprogrammed cells with acquired pluripotency

263 Mary Ann Liebert, Inc.,Tissue Engineering

1 24 4.065

(accept)

4 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)5 Isolation of pluripotent adult stem cells discovered from tissues derived from all

three germ layers 23


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- 2 -

26 3 17

26 3 28

31

26 3 31.

I.

II.


6/82

- 3 -

V.

26 3 31 7 16

.

.

Nature Tissue

1.

1)

26 4

24 5 29 2

6 26 4 30 5

28 6 11

2)

3)

26 6 22

4) 26 6 27

B

2.

1)

26 4 16 6

19

2)

26 4 11 5

20 23 2 9

6 C


7/82

- 4 -

DE

FGHIJK L

3)

26 5 2

M

4)

26 5 21

6 3 23 2 25

NA O

5)

26 6 18

23

1 11

P

6)

3.

1)

26 5 21

Q

2)

R

4.

1)

26 5 8

S

2)

T


8/82

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5.

1)

26 5 9 5 23 2

CDB

U

2)

U

3) 26 4

24 6 207

26 5 8 6 25

6.

National Institutes of HealthNIHW

XZen-Bio, Inc.Zen-Bio

Harlan

7.

1)

Tissue

2 4 Tissue

Tissue

Tissue

7 V


9/82

- 6 -

2)

3)

U

4)

U

5)

.2.(3).c.(c)

.2.(3).c.(a)

6)

7) .2. 3)a.


10/82

- 7 -

8)


11/82

- 8 -

2

.

V.

20

4 1

5

9 1

6

21

1

3

4 1 2

8

22

6 30 Tissue Tissue

First Author

SRQ 1

Corresponding AuthorT

8 U

9 30 Tissue Tissue

11 11

11 13

11 17

12 8

R T 23

1 11

2 8

2 9

2 25

3 15

4 CDB

25

3 10 Nature Nature


12/82

- 9 -

12 20 Nature Nature

26

2 Nature

3 31


13/82

- 10 -

I.

1.

1)

8

910

a.

1 1 1.1 1.5 6

(a)

i.

11

8 45 5 6 48 21

2 1 15

2 1 1

2

9

10

6

6

11 NIH NIH

NIH


14/82

- 11 -

ii.

iii.

12

iv. NIH

v. 32

13

NIH21

(b)

.1.(1)a.(a)

i.

ii.

1

105NIH

2574 3

642512 13

32 1

35

35


15/82

- 12 -

4500

1 80 20 80

b. 25 Fig. 1

(a)

i.

ii.

14

iii.

iv. WW

v.

32

W21

(b)

.1.(1)b.(a)

i.

14 C-kit positive stem cells


16/82

- 13 -

ii.

c.

26 Fig. 2

1

1

(a)

1

i.

ii. 1

1

1

1516

iii.

1

1

1

15

14 6 28 55 4 837

16 1

1

21


17/82

- 14 -

iv.

XX

v. 32

1

X21

(b)

1.1.(1)c.(a)

i. 1

ii.

1

1

d.

71 Fig. 15 2

2

(a)

2

i.

ii. 2 2

iii. 2

2

2


18/82

- 15 -

iv.

XX

v. 32

2

X21

(b)

2.1.(1)d.(a)

i. 2

ii.

2

2

e.

73 Fig. 17 3

3

(a)

3

i.

ii. 3 3

iii. 3

3

3


19/82

- 16 -

iv.

XX

v. 32

3

X21

(b)

3.1.(1)e.(a)

i. 3

ii.

3

3

f.

46 2 2.6References 24 3158

3

3.6

References

76

4

4.6

References

1 49 93 5 5.6References

(a)

i.

17

17 12 1


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ii.

iii.

iv.

v.

32

21

3 5

(b)

.1.(1)f.(a)

i.

ii.


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3 5

g. 53 Fig. 10

18

(a)

i. Muscle

(i)

1 1

1 1

(ii) 1

1

(iii) 1

1

(iv) Zen-Bio

1 Zen-Bio

1

19

(v)

32

18

19

Zen-Bio

1

1


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- 19 -

Zen-Bio 1 21

ii. hepatocyte

(i)

2 2

2

2

(ii)

2

2

(iii) 2

2

(iv)

2

2

(v) 32

2

21

(b)

.1.(1)g.(a)

i.

ii.

1 2


23/82

- 20 -

2021(c)

in vitro6

.2.(3)

.2.(3)f.(b)

h. 86 Fig. 20

(a)

i.

20

21

6


24/82

- 21 -

ii.

iii.

iv. HarlanHarlan

v. 32

Harlan 21

(b)

.1.(1)h.(a)

i.

ii.

2)

a.

42

Fig. 7

2Oct4/DAPI

SSEA-1/DAPIFigure 7 Pluripotent marker

expressions/Spheres at day 5 expressed pluripotent cell markers Oct4 and

SSEA-1. 2


25/82

- 22 -

22

b.

57

Fig. 14

3

3Figure 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 11B. Optimistic pressure

13destroy mature cells.

3

A. Cell sorterB. Optimistic pressureC. Trituration

using thin-glass pipetteB. Optimistic

pressure

B. Optimistic pressure

Optimistic pressure

2324

b. 30 2 2.3.2only small

cells.

22 Fig. 7 Fig. 6 GFig. 7 Fig. 8

Oct4 Fig. 723 optimistic pressureosmotic pressure

24 Optimistic pressureOsmotic pressure

B. Osmotic pressure

2

2.2.1


26/82

- 23 -

Fig. 3

c. 33 2 2.3.6three germ

layers was examined.

Fig. 8

25

d. 36 2 2.5The 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 3Neural cells ectoderm

lineage)

13

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

in vitro

Fig. 17i

- A,B,CFig. 17

Fig. 17

25 1 4 4.3.2662


27/82

- 24 -

4)

Tissue

a.

54 Fig. 11 3

3 3.3.1 4 6The addition(a)

of 14into endodermal tissue.

Tissue

611 11 3The addition of 11

into endodermal tissue.

Fig. 4

Tissue(b)

Ectoderm Tissue26

Tissue

Mesoderm Tissue27(c)

Tissue

Endoderm Tissue28(d)

Tissue

Tissue

Tissue

Tissue

b. 73 Fig. 17 27

26 Fig. 4 B27 Fig. 4 E28 Fig. 4 H


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4 4.3.3(a)

Tissue611 14Spinal spheres, myospheres, 612 4

procured from BM.

Fig. 5

Tissue(b)

spinal cord Tissue29

Tissue

muscle Tissue30(c)

Tissue

lung Tissue31(d)

Tissue

Tissue Fig. 5(e)

32 Tissue Fig. 5

Tissue

Tissue

Tissue

c. 68 4 4.3.4 6 4Tissue generated

from spinalspheres 10 1duct like tissue endoderm)

29 Fig. 5 A30 Fig. 5 C31 Fig. 5 B32 Tissue Fig.4

Map2MyoD


29/82

- 26 -

Fig. 18).

(a)

Fig. 18

Tissue 613 4 2Tissue generated from

spinal spheres 9 5duct-like tissue (endoderm; Fig.

6Cv, Cvi).

Fig. 6 Ai B Aii C

Tissue(b)

Tissue Fig. 6 Ai

B Aii 14

Fig. 18

7

Tissue

Tissue

Tissue

d.

74 Fig. 18

4 4.3.4 6 4Tissue(a)

generated from spinalspheres 8 2duct like cuboidal

epithelium (endoderm) (Fig.18). 8 3Tissue

generated from myospheres 10 1duct 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 5duct-like


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

Fig. 6 Ai

B Aii C Tissue(b)

Tissue

Tissue

Tissue

Tissue

Tissue

e.

75

Fig. 19

4 4.3.4 10 2Tissue(a)

generated from pneumospheres 11 7cartilage

(mesoderm) (Fig.19), gland (ectoderm) (Fig.19).

Tissue 613 9 6Tissue generated from

pneumospheres 1 3cartilage (mesoderm; Fig.

6Diii, Div), and gland (ectoderm; Fig. 6Dv, Dvi).

Fig. 6 Aiii D

Tissue(b)

Tissue

Tissue

Tissue

Tissue

Tissue


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5)

33

a.

29 2 2.2.1 14C. Trituration using

thin-glass pipette

17

by mechanical stress.

3

A. Cell sorterB. Optimistic pressureC. Trituration

using thin-glass pipetteC. Trituration

using thin-glass pipette

pipetting

b.

81 5

5

34

c. Curriculum VitaePatent

"Patent""Haruko

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

6)

33 34 5 CDB


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2.

1)

35

2 5

a.

2 4

2 4Tissue

Tissue

Tissue

(a)

S(b)

35


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36

21 22 (c)

37

2 4

b.

5

51)

Aggregation Method

Injection Method 382)

393)

40 4)

GFPImmunohistochemistry

41

Tissue

(a)

36

37 38 5 5.2.1 5.3.139 5 5.3.240 5 5.2.2 5.3.341 5 5.2.3 5.3.3


34/82

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Aggregation Method Injection Method

CDB U

Black6-GFP

22 8 9

10

U

2 22

8 910

8

105 20

22 8 9 10

22 8 9 10 U

(b)

22 8 9 10

22 12 CDB

22 12 21

GFP

U 22 12

U

(c)

22 9 9 11

17


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GFP

U 22 9 9 11

17

22 10 14

GFP

GFP(d)

Immunohistochemistry

U 22 12 2GFP

GFP

Fig. 26

c.

2 4

Tissue TissueS

5

UU

2) Tissue

a.

TissueSYRQ T

SYRQ

T


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- 33 -

SSYRQ

TTissue

Tissue

Tissue

b.

Tissue

Tissue

TissueTissue

5

22

422()

22

Curriculum

VitaeOriginal Papers Tissue

Tissue

Tissue Tissue

43

42 43 S


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- 34 -

Tissue

3)

a.

26 5

28

b.

(a)

13

44

2 5(b)

5

(c)

44

4500

32

1

2 3


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- 35 -

Fig. 7(d)

Fig. 10(e)

Figure(f)

2 Fig. 18 Fig. 19

Figure 3 Fig. 16Fig. 17

Fig. 18

c.

23 1 7(a)

3 Figure

45

i. 23 1 7

23

1 11

ii. 23 1 11

R

iii.

4647 48

3

3

45


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3

3 2 FigureFig. 18Fig. 19

1

FigureFig. 16Fig. 17 Fig. 18

3

46

iv.

4647 48

v.

R

4647 48

3 Figure

(b)

.2.(3)c.(a)

3 Figure

2 Figure

46 46 Fig. 18

Fig. 18 47

Fig. 17 48

Fig. 19 Fig. 16


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.2.(3)c.(a)iii.Fig. 16Fig. 17 Fig. 18

Figure 3

Figure 2

(c)

47

i. 22 11 13 1

22 11

13

1

4 5

2

ii.

2

Fig. 18 Fig. 19

iii. 23 1 11

Fig. 17

iv.

v.

22 11

47


41/82

- 38 -

.2.(3)c.(a)(b)

d.

.2.(3)c.

first author(a)

Tissue Tissue

Tissue

.1.

(b)

.1.(c)

(d)

Fig. 6Fig.

12 IFig. 17

(e)

U


42/82

- 39 -

e.

(a)

26 4 30

5 27

1

Nature

2

1

optimistic pressure(b)

optimistic pressureosmotic

pressure

48

48 P


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optimistic

pressureosmotic pressure

1(c)

2 5

5

5

f.


44/82

- 41 -

49

(a)

i.

ii.

iii.

3 48 57

3 38

58 62

iv.

49

26 6 24


45/82

- 42 -

(b)

i.

Fig. 11

Fig. 12

Fig. 14Fig. 11

1214

ii. 3 3.3.1 1When

representative bone marrow derived 4 5

MyoD(mesoderm) and alpha-fetoprotein (AFP, endoderm) (Fig. 10).

Map2MyoD AFP

Tissue


46/82

- 43 -

611 4When representative BM-derived 8 1

MyoD (mesoderm), and AFP(endoderm).

Tissue

Tissue Fig. 4 A

Tissue Fig. 4 A

iii.

Tissue Fig. 4

A

iv.

3

NeuronMuscleHepatocyte

g.

.2.(3)f.

.1.

50

.1.

50 .1.


47/82

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.2.

.2.(3)e.

1 2 3

1 2

3

1

2 3

h.

.2.(3)f.

.1.

i.

.2.(3)f.


48/82

- 45 -

.

4)

a.

41

Fig. 6

Fig. 6 2 2.3.4 2

Tissue 609

25 6Spheres of up to 150 m 39five generations

in this experiment.

Fig. 1

TissueFig. 6 Tissue

Fig. 1

Fig. 6(A)(B)(D)(J) Tissue Fig.

1(A)(B)(D)(J)

51Tissue

51 26 5 28


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b.

43 Fig. 8 72 Fig. 16

TissueTissue

T

TTissue

TissueRetraction

TissueTissue

Tissue

Fig. 8 Fig. 16


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II.

1.

Tissue

.3.(5)

2.

1) 23 1

.1.

23 1

2) 23 1


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23 1

3)

1

)

a.

23 1

52

5354

5556

b.

(a)

52

23 1

53 454

255 569 2 3

4344355 174 2

56


52/82

- 49 -

57

(b)

Tissue

58

c.

.2.(3)a.

59

d.

.2.(3)

57

58 59

6 174

42 11

8 21 9 1197 18 1 2


53/82

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.2.(3)b.

.2.(3)b.

1

2 3

1 2 3

4)

2

)

a.

23 1

60

61

b.

.2.(3)

(a)

60 189

310

11461


54/82

- 51 -

i.

22

2()

22

ii.

iii.

iv.

62

v.

(b)

i.

62

3


55/82

- 52 -

ii.

iii.

iv.

v. 22

(c)

i.

ii.

iii.

.1.

c.

.2.(4)b..2.(3)


56/82

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(a)

.1.

1

4500

1 80 20 80

1

63

.2.(4)b.

(b)

.1.

1

1

1

.2.(4)b.

63


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1(c)

.1. 1

1 1 1

1

1

1

.2.(4)b. 1

1

2(d)

.1. 2

2

.2.(4)b. 2

2

3(e)

.1. 3

3

.2.(4)b. 3

3


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(f)

.1.

.2.(4)b.

3.

11

1 2 3

23 1


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V.

1.

1)

7 2

19 2

1

3

2)

10

2

64 1

2

2.

.1.

64 22 6

21 4 8


60/82

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3 1

3.

1)

a.

65

3 16(a)

18 1(b)

65 .3.(1)a.(m).3.(1)a.(n)


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18

4Q R

18 4(c)

20 3

1

66Q

R

20 5R S(d)

S

20 9 21 3(e)

6 21 4 1 21 8

5

T S

(f)

21 8

21 8

66


62/82

- 59 -

21 8(g)

23 3

67

U

1

QR U

22 10(h)

22 11 11

22 11(i)

22 11 13(j)

(k)

1

67 22 43


63/82

- 60 -

(l)

4

23 1 7(m)

68

22 11(n)

23 1 7

221569(o)

.1.(p)

1 2 3

b.

.3.(1)a.

(a)

68 1

5

69 20 28 21 21 23

18 24 22 25 28


64/82

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22 1123 1 7

.1.

(b)

.1.

(c)

.1.


65/82

- 62 -

70

(d)

.3.(1)b.

71

2)

.1.

a.

.3.(1)a..3.(1)b.

72

70

71

72 22 6

20 13 21 9 23 7 24 7

25 10 1


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22 6 22 6

2

b.

.3.(1)a..3.(1)b.

73

74

4.

73

74

2


67/82

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.

1.

1)

5 2

2

14 1

4

15

3 22

2()

22

2)

3

12 1

12 2 3

3 1

12 4

3)

22

22

a.


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b.

c.

75

d.

e.

3 2

3 2

f.

75


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2.

1)

.1.(2)

3 1

2)

3 1

76

3)

a.

76

644


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3 1

b.

(a)

30 1

(b)

(c)

(d)

15

(e)

(f)


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4)

a.

3 1

b.

(a)

11

(b)

(c)

(d)

(e)


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3.

1)

a.

77

23 1 7(a)

78

R(b)

23 1 25

23 2 3

23 2 9(c)

23 2 9(d)

77 IV.3.(1)a.(a)

78 1

5


73/82

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(e)

(f)

.1.(g)

1 2 3

b.

.2.(1)

(a)

.1.

(b)


74/82

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(c)

(d)

.3.(1) b.

79

2)

a.

23 1 7(a)

R(b)

79

.3.(1)


75/82

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23 1 25

23 2 3

23 2 9(c)

23 2 9(d)

(e)

(f)

.1.(g)

1 2 3

b.

.2.(2)

(a)


76/82

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.1.

(b)

(c)

(d)

80

3)

.2.(3)b.

80


77/82

- 74 -

.1.

4)

.2.(4)b.

5)

.1.

a.


78/82

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b.

.1.

81

82

81

82


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c.

.1.

d.

.1.

22

83

e.

83


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4.

.1.


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I.

Tissue

2

1

2


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140717 Committee Report

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Transcript of 140717 Committee Report