Stem cell transplantation with CABG

Cellular Cardiomyoplasty
using
Bone Marrow-derived
Stem Cells
Cardiothoracic Sciences Center
All India Institute of Medical Sciences
New Delhi, India

CELLULAR CARDIOMYOPLASTY
WWW.AIIMS.AC.IN
Congestive Heart Failure
A global concern
In USA > 5 Million people have heart
failure
35% asymptomatic
50% stable – on oral drug therapy
10 – 15 % advanced heart failure
Heart transplantation best therapy
Only 2500 hearts available in USA each
year

WWW.AIIMS.AC.IN
Complications &
causes of death in CHF
Progressive Heart Failure
Sudden cardiac death

WWW.AIIMS.AC.IN
Alternatives & limitations
Medical Therapy Limited benefit
Revascularisation Essential
Assist devices Expensive
Infections
Cardiac
transplantation
Donor scarcity
Immunosuppression

Cellular Cardiomyoplasty
Is it an answer?

WWW.AIIMS.AC.IN
Cellular cardiomyoplasty:
Concept
Growing interest as a potential new means of
improving prognosis of heart failure
Assumption
LV dysfunction largely DUE to loss of critical number
of cardiomyocytes
Partly reversed by implantation of new contractile
cells into post infarction scars
Cell types
Autologous skeletal myoblasts
Bone marrow stem cells
Autologous origin
Cardiomyocyte / endothelial trans - differentiation potential

WWW.AIIMS.AC.IN
Stem Cells
Totipotent : capacity to turn into any type
of cell in the body, including placenta.
Pluripotent : can turn into any cell other
than the placenta.
Multipotent : can form a limited number of
cells. e.g. HSC

WWW.AIIMS.AC.IN
CELLULAR CARDIO MYOPLASTY
CELL SOURCES & LIMITATIONS
CELLSOURCE ETHICAL
PROBLEMS
ACQUISITION
CONCERNS
REJECTION ONCOGENICITY
FEATAL CARDIO
MYOCYTES
YES YES YES NO
ADULTCARDIO
MYOCYTES
NO YES NO YES
SKELETAL
MYOBLAST
NO YES NO NO
EMBRYONIC
STEM CELL
YES YES YES YES
MARROW
STROMAL CELL
NO NO NO NO
JTCVS NOV 2000

WWW.AIIMS.AC.IN
Bone Marrow Stem Cells :
Plasticity & Differentiation

WWW.AIIMS.AC.IN
PLASTICITY OF
HEMATOPOIETIC STEM CELLS

WWW.AIIMS.AC.IN
Hematopoietic Stem Cells
Stem cell markers
CD34+
Lin-
C-Kit +
CD133+

WWW.AIIMS.AC.IN
Myocardium Repair: The best choice
Cardiocytes
Taylor et al. 1998
Skeletal myoblasts
Menasche et al. Lancet,2001
Bone marrow stem cells
Stamm et al.Lancet,2003
Wang et al. Circulation, 2002
Orilic et al. Nature, 2001
Toma et al, Circulation2001

WWW.AIIMS.AC.IN
Various modalities of delivery of
stem cells used:
Direct injection
Percutaneously:
Intracoronary injection
Endocardial delivery
Intravenous injection

WWW.AIIMS.AC.IN
Preop. investigations:
Echocardiography- 16 segment
analysis
Stress Thallium- 20 segment
analysis
Coronary angiography
Left ventriculography- 5 segment
analysis

WWW.AIIMS.AC.IN
Echo short axis view showing an
anterior infarct:

WWW.AIIMS.AC.IN
Stress Thallium: Polar maps of a
patient with septal ischemia
White area
indicates
reversible
ischemia

WWW.AIIMS.AC.IN
Stress Thallium: Polar maps
depicting large anteroseptal scar
Black
area
indicates
scar

WWW.AIIMS.AC.IN
Stress Thallium: 3D images
Anteroseptal Scar
Normal study

WWW.AIIMS.AC.IN
Stress Thallium: Quantitative 20
segment analysis being performed:

WWW.AIIMS.AC.IN
Stress Thallium
Quantitative analysis:

WWW.AIIMS.AC.IN
LV angiogram
showing inferior infarct:

WWW.AIIMS.AC.IN
LV angiogram
showing apical aneurysm:

WWW.AIIMS.AC.IN
Example of a LV with large area of
Anterolateral & apical akinesia:

WWW.AIIMS.AC.IN
LV with a large anterolat-apical
aneurysm:

WWW.AIIMS.AC.IN
LV angiogram documenting a large
thrombus at LV apex:
Thrombus

WWW.AIIMS.AC.IN
Cellular Cardiomyoplasty: AIIMS study
Patients with CAD undergoing CABG &
having reduced LV function with an area
of non-viable myocardium
Bone marrow obtained from same patient
& processed to isolate stem cells
Cells injected directly into myocardium at
the end of CABG procedure

WWW.AIIMS.AC.IN
AIIMS study: Patients
No. of patients: 32
Period: Feb 03 to Dec 04
Age:
mean: 51.76.5 years
range: 42-62 years
Sex: 29 males, 3 female

WWW.AIIMS.AC.IN
AIIMS study: patients
Diabetics: 14%
Hypertensives: 43%
History of smoking: 36%
History of MI: 86%

WWW.AIIMS.AC.IN
AIIMS study: patients
Basal NYHA class:
mean: 2.9  0.7
range: 2-4
Basal Left ventricular status:
Akinetic areas: all patients
In anterior wall in 86%
Basal LVEF: 33  16%

WWW.AIIMS.AC.IN
AIIMS study: procedure
Bone marrow obtained at the start of
CABG surgery from sternum
Bone marrow sent for stem cell
preparation while CABG performed
Processed stem cells injected in infarcted
areas at the end of CABG procedure,
including non-revascularisable areas

WWW.AIIMS.AC.IN
Bone Marrow Aspiration

WWW.AIIMS.AC.IN
Bone Marrow Collection
(in heparinized syringes)

WWW.AIIMS.AC.IN
Separation of Stem Cells/MNCs
Dilution of the Bone marrow
Ficoll density gradient centrifugation
Washing of MNC
Viability of the MNC
Cell count
-Strauer et al. Circulation, 2002
-Galinanes et al. AHA, 2002

WWW.AIIMS.AC.IN
Collection of
Bone Marrow Aspirate Layering of Bone Marrow

WWW.AIIMS.AC.IN
Bone Marrow Aspirate
Ficoll
RBC & Granulocyte
Mononuclear cells
Platelets
Before centrifugation After centrifugation
Separation of Blood Cells

WWW.AIIMS.AC.IN
Stem cells/MNCs
Normal Saline
with Heparin

WWW.AIIMS.AC.IN
Dead Cell
Dead Cell
Viable cell
Viability of Stem Cells-Trypan Blue Dye

WWW.AIIMS.AC.IN
(Under 100X; Oil immersion)
Stem Cells : MNC - Giemsa Stained
(Under 40X)

WWW.AIIMS.AC.IN
Cell Counting Chamber

WWW.AIIMS.AC.IN

WWW.AIIMS.AC.IN
AIIMS study: Stem Cell details
Volume of bone marrow harvested: 348 ml
Cell count: 1522 million per ml
Mononuclear cell percentage: 892%
Viability: 991%
Final volume: 125 ml
CD 34 count: 1.21 0.6

WWW.AIIMS.AC.IN
Peri scar Injection

WWW.AIIMS.AC.IN
Intra scar Injection

WWW.AIIMS.AC.IN
Results
Grafts: 2.8  0.6
(range: 2-4)
Additional procedures:
Dor’s procedure: 2
LV clot removal: 1
Post MI VSD closure: 1
No. of injections per patient: 25-48
Amount injected: 0.25 cc per sq cm

WWW.AIIMS.AC.IN
Results
Hospital stay: 6-11 days
Post-op period: uneventful
No peri-op or post-op mortality

WWW.AIIMS.AC.IN
Results
Mean duration of follow-up:
5.5  3 months
NYHA:
Improved significantly
1.25  0.6 (vs 2.9  0.7 at baseline)
P < 0.001

WWW.AIIMS.AC.IN
2.9
1.25
0
1
2
3
Basal On Follow-up
NYHA

WWW.AIIMS.AC.IN
Echocardiographic LV dimensions
End-diastolic:
remained stable
143  39 ml (vs 140  37 at baseline) (P=NS)
End-systolic:
remained stable
86.5 38 (vs 94  32 at baseline) (P=NS)

WWW.AIIMS.AC.IN
Echo LV ejection fraction analysis:
Evidence of improvement
41  9% (vs 32  12% at baseline)
(P=0.05)

WWW.AIIMS.AC.IN
32
41
0
20
40
60
Basal On Follow-up
Echo LV Ejection Fraction

WWW.AIIMS.AC.IN
Overall more segments showed
improvement than deterioration:
Improvement: mean 3.7  2.6 segments
No change: mean 10.0  1.6 segments
Worsening: mean 2.3  2.6 segments
Total score:
33.7  2.1 (vs 36.0  4.0 at baseline) (P=NS)
Echocardiographic 16 segment analysis

WWW.AIIMS.AC.IN
Echo evaluation of injected
infarcted segments
Segments injected: 4.1  2.0
Segments showing improvement: 2.3
 1.7
Others remained same
None worsened
56.1 % of infarcted areas injected
with stem cells improved.

WWW.AIIMS.AC.IN
56.1
43.9
0
0
20
40
60
Percentage
Improved Same Worse
Effect on Infarcted Segments Injected
with Stem Cells: Echo Analysis

WWW.AIIMS.AC.IN
Stress Thallium 20 segment analysis
No. of scarred segments reduced:
From 5.4  2.7 to 4.6  2.6
No. of normal segments increased:
From 6.2 3.9 to 8.2  4.1
More segments showed improvement:
Improved: mean 5.8 segments
No change: mean 14.2 segments
Worsened: mean 0 segments

WWW.AIIMS.AC.IN
6.2
8.2
0
5
10
Basal On Follow-up
Stress Thallium: Normal Segments

WWW.AIIMS.AC.IN
5.4
4.6
4
4.5
5
5.5
Basal On Follow-up
Stress Thallium: Scarred Segments

WWW.AIIMS.AC.IN
Stress Thallium: Injected infarcted
segment analysis
Segments injected: 7  2
Segments improving: 1.8  1.9
Others remained same
None worsened
26% of injected infarcted segments improved

WWW.AIIMS.AC.IN
25.7
74.3
0
0
50
100
Percentage
Improved Same Worse
Effect on Infarcted Segments Injected
with Stem Cells: St. Thallium Analysis

WWW.AIIMS.AC.IN
AIIMS study: follow-up results
Holter evaluation at follow-up:
No significant arrhythmias noted

WWW.AIIMS.AC.IN
Dyskinesia
Akinesia
Hypokinesia
Normal
Dyskinesia
Akinesia
Hypokinesia
Normal
Angiographic LV segment analysis
Baseline Follow-up

WWW.AIIMS.AC.IN
Basal LV of a patient (HD):
Anterolateral, apical
and infero-apical
akinesia

WWW.AIIMS.AC.IN
LV after CABG+stem cell
implatation:
Only a small area of
high anterolateral
akinesia
Remaining walls
contracting well

WWW.AIIMS.AC.IN
Stress Thallium: before & after
CABG+stem cell implantation
SL, Date of surgery: 28-4-03
Pre 25-4-03 Post 23-5-03
Reduced
area of scar
& ischemia

WWW.AIIMS.AC.IN
KS, Date of surgery: 26-2-03
Pre Post
Normal
viability &
perfusion in
previous
scar

WWW.AIIMS.AC.IN
PK
Pre Post
Reduced
area of
scar

WWW.AIIMS.AC.IN
Conclusions
Bone marrow derived stem cell
transplantation during CABG is feasible
and safe.
Bone marrow obtained from sternum at
the time of CABG provides adequate
number of stem cells
Early data is suggests that this procedure
may be beneficial in patients with scars /
recent infarct in left ventricle.
Further studies are needed

WWW.AIIMS.AC.IN
Stem cell implantation
combined with
percutaneous coronary intervention

WWW.AIIMS.AC.IN
Basal angiogram

WWW.AIIMS.AC.IN
Lesion dilated with an over-the-wire
balloon catheter:

WWW.AIIMS.AC.IN
Stem cells delivered through balloon
catheter lumen (PTCA wire removed):

WWW.AIIMS.AC.IN
Wire passed again & balloon catheter
removed:

WWW.AIIMS.AC.IN
Final result after stenting of lesion:

Stem cell infilteration in
diabetic patients
Recently performed on 2 patients

WWW.AIIMS.AC.IN
Catheter in Position

WWW.AIIMS.AC.IN
Hepatic Artery Gastroduodenal Artery
Pancreatico-
duodenal As.

WWW.AIIMS.AC.IN
Stem Cell Injection

WWW.AIIMS.AC.IN
Hepatic Artery Gastroduodenal Artery
Pancreatico-
duodenal As.
Vessel status after Injection

WWW.AIIMS.AC.IN
Contributing Departments:
CTVS
Cardiology
Nuclear Medicine
Radiology
Haematology

Stem cell transplantation with CABG

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Stem cell transplantation with CABG

Similar to Stem cell transplantation with CABG (20)

More from India CTVS

More from India CTVS (20)

Recently uploaded

Recently uploaded (20)

Stem cell transplantation with CABG