slide1
Download
Skip this Video
Download Presentation
MANUEL Mª MAZO VEGA

Loading in 2 Seconds...

play fullscreen
1 / 14

MANUEL Mª MAZO VEGA - PowerPoint PPT Presentation


  • 75 Views
  • Uploaded on

U n i v e r s i d a d d e N a v a r r a. CENTRO DE INVESTIGACIÓN MÉDICA APLICADA. TRANSPLANTATION OF MESENCHYMAL STEM CELLS EXERTS A GREATER LONG-TERM EFFECT THAN BM-MNC IN CHRONIC MYOCARDIAL INFARCTION IN RAT. MANUEL Mª MAZO VEGA. Cardiovascular diseases: First cause of mortality

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' MANUEL Mª MAZO VEGA' - jon


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Universidad deNavarra

CENTRO DE INVESTIGACIÓN MÉDICA APLICADA

TRANSPLANTATION OF MESENCHYMAL STEM CELLS EXERTS A GREATER LONG-TERM EFFECT THAN BM-MNC IN CHRONIC MYOCARDIAL INFARCTION IN RAT

MANUEL Mª MAZO VEGA

slide2

Cardiovascular diseases:

    • First cause of mortality
    • Myocardial infarction: 12,6%

MATERNAL AND PERINATAL COND, NUTRITIONAL STATE

30%

CANCER+RESP DISEAS +DIABETES

22%

CARDIOVASCULAR DISEASES

30%

INJURIES 9%

OTHER CHRONIC DISEAS. 9%

MYOCARDIAL INFARCTION

The world health report 2004, World Health Organization

slide3

PHARMACOLOGICAL

SURGICAL

MYOCARDIAL INFARCTION: TREATMENTS

REGENERATIVE

Gene Therapy

Cell Therapy

Nitrates

Aspirin

ACEi

ARB

Aldosterone antagonists

Estatins

Beta-Blockers

Inflammatory cytokines antagonists

Neutral endopeptidase inhibitors

Reperfusion

Transplant

slide6

SPRAGUE-DAWLEY RAT (+Cyclosporin)

Phenotype

Differentiation

Histological Analysis

Infarct

Implant (106 cell)

RT1A+

CHONDROCYTE

-30 d

+0 d

+7 d

+14 d

+30 d

+90 d

RT1B-

CD44+

Eco

Eco

microPET

Eco

microPET

BM-MNC GFP+

ADIPOCYTE

CD31-

CD73+

MSC GFP+

CD45-

CD90+

OSTEOCYTE

EXPERIMENTAL DESIGN

GFP+ S-D RAT

5-6 weeks

slide7

PRE-IMPLANT

3 MONTHS

RESULTS: CARDIAC FUNCTION

*

60

*

50

40

% LVEF

30

20

10

0

MEDIUM

BM-MNC

MSC

slide8

PRE-IMPL

3 MONTHS

RESULTS: TISSUE METABOLISM

A

C

85

**

80

MEDIUM

% 18F-FDG UPTAKE (ALL SEGMENTS)

75

70

65

60

MEDIUM

BM-MNC

MSC

B

BM-MNC

*

60

55

% 18F-FDG UPTAKE (INF. SEGMENTS)

50

45

40

MSC

35

MEDIUM

BM-MNC

MSC

slide9

1 WEEK

2 WEEKS

1 MONTH

3 MONTHS

C

A

B

D

MEDIUM

G

E

F

H

BM-MNC

K

I

J

L

MSC

RESULTS: ENGRAFTMENT

slide10

MEDIUM

MEDIUM

BM-MNC

BM-MNC

MSC

MSC

RESULTS: INFLAMMATION

C

D

A

B

CD68TOPRO3

CD68TOPRO3

CD68TOPRO3

**

400

300

INFARCT CD68+/mm2

200

100

0

1 WEEK

2 WEEKS

1 MONTH

MEDIUM

BM-MNC

MSC

**

G

H

F

E

GFP CD68TOPRO3

GFP CD68TOPRO3

GFP CD68TOPRO3

**

2500

2000

**

PERI-INFARCT CD68+/mm2

1500

**

1000

**

500

0

1 WEEK

2 WEEKS

1 MONTH

MEDIUM

BM-MNC

MSC

J

L

M

I

K

TOPRO3

GFP

CD68

MERGED

MERGED

slide11

A

B

*

*

*

RESULTS: INFLAMMATION

slide12

RESULTS: MECHANISMS OF ACTION

C

D

A

B

CAV1DAPI

CAV1DAPI

CAV1DAPI

*

1200

900

CAPILLARIES/mm2

600

300

0

MEDIUM

BM-MNC

MSC

MEDIUM

BM-MNC

MSC

**

G

H

F

E

αSMADAPI

αSMA DAPI

αSMA DAPI

**

3

**

2,5

2

% SM-POSITIVE AREA

1,5

1

0,5

0

MEDIUM

BM-MNC

MSC

MEDIUM

BM-MNC

MSC

K

L

J

I

25

20

*

15

% INFARCTED LV

10

5

0

MEDIUM

BM-MNC

MSC

MEDIUM

BM-MNC

MSC

O

P

N

M

75

70

*

65

% CVF

60

55

MEDIUM

BM-MNC

MSC

50

MEDIUM

BM-MNC

MSC

slide13

150

150

100

100

50

50

PCNA αSMATOPRO3

PCNA αSMATOPRO3

PCNA αSMATOPRO3

PCNA αSMATOPRO3

PCNA αSMATOPRO3

PCNA αSMATOPRO3

PCNA αSMATOPRO3

PCNA αSMATOPRO3

0

0

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

GFPPCNAαSMATOPRO3

200

200

150

150

100

100

50

50

0

0

50

50

40

40

30

30

20

20

10

10

0

0

RESULTS: MECHANISMS OF ACTION

PERI-INFARCT

INFARCT

A

B

PERI-INFARCT

INFARCT

1 WEEK

2 WEEKS

1 WEEK

2 WEEKS

#

**

BM-MNC

**

**

PCNA+CAV1+/mm2

PCNA+CAV1+/mm2

**

**

**

**

**

PCNA CAV1TOPRO3

PCNA CAV1TOPRO3

PCNA CAV1TOPRO3

PCNA CAV1TOPRO3

CAV1+PCNA+

1 WEEK

2 WEEKS

1 WEEK

2 WEEKS

MSC

GFPPCNACAV1TOPRO3

GFPPCNACAV1TOPRO3

GFPPCNACAV1TOPRO3

GFPPCNACAV1TOPRO3

##

##

##

##

**

**

BM-MNC

**

PCNA+αSMA+ (MYOFIB)/mm2

PCNA+αSMA+ (MYOFIB)/mm2

**

MYOFIB (αSMA+) PCNA+

1 WEEK

2 WEEKS

1 WEEK

2 WEEKS

MSC

BM-MNC

PCNA+αSMA+ (SMC)/mm2

*

PCNA+αSMA+ (SMC)/mm2

SMC (αSMA+) PCNA+

1 WEEK

2 WEEKS

1 WEEK

2 WEEKS

MSC

BM-MNC

MSC

slide14

CONCLUSIONS

  • Treatment with bone marrow stem cells (BM-MNC or MSC) induced a long-lasting (3 months) improvement in cardiac function. Moreover, animals injected with MSC showed an increase of tissue metabolism, which was associated with a decreased infarct size and collagen content and a higher degree of revascularization.
  • The benefits observed after bone marrow stem cell transplantation were possibly due to paracrine mechanisms involved in angiogenesis and host cell proliferation and not through direct cell contribution.
ad