WIEF-AFF
ROUNDTABLE 2015
Tokyo, Japan
26 May 2015

Regenerative Medicine
Goal:- To restore organ +/- tissue function- For pts with serious injuries or chronic disease’
where the body unable to heal & restore function

Needs:
i. Patients with serious injuries & chronic diseaseii. Shortage of organ donorsiii. Ageing population

Regenerative Medicine
Needs for Malaysia:
i. Heart Failure is end-stage of heart disease.
ii. Heart transplantation- Shortage of organ donors- problems of rejection & infectioniii. LV assist device – costly
iv. Stroke – disablingv. Peripheral arterial diasease- amputation & loss of limb

Stem cell therapy – promising potential

Regenerative Medicine
Stem Cell Therapy:
Uses stem cells:- Stem cells are able to go to damaged areas / organs& regenerate new cells and tissues
 Restoring function of failing / impaired tissues

Bone Marrow Stem Cells- Mesenchymal Stem Cells MSC- Bone Marrow Mononuclear Cell BMMNC

Umbilical Cord:- the Best Source for allogeneic Mesenchymal Stem Cells

Stem Cell Therapy in Malaysia
Stem Cell Therapy in Malaysia:
Different stages in different medical specialty.
- haematology

Stem Cell Therapy in Cardiovascular Disease:“early/preliminary” stages.
- Using BM Stem Cells

Stem Cell Therapy in Malaysia
Stem Cell Therapy in Cardiovascular Disease:
9 studies. ‘small’ studies.
3 presented at international meetings
1 unpublished6 publications in international journals

Stem Cell Therapy in Malaysia
1. 4th European Association of Cardiothoracic Surgeon EACTS/ ESTS Joint Meeting, Barcelona, Spain 24 – 28 Sept 2005:“Direct Intramyocardial Injections Using High Cell Count ofAutologous Bone Marrow Stem Cells as a Sole Therapyfor Severely Ischaemic Heart Disease – Beyond One Year”- Dr Mohd Azhari Yakub, Mr Hj Mohd Isham Hj Jaafar, Mr Reiji Hattori
N= 8 patients.
Symptoms improved with improved functional class.
But no significant objective improvements eg Ejection Fraction EF
Technetium scan appeared to show improvement.
Unfortunately at that time we did not have Cardiac MRI.

Stem Cell Therapy in Malaysia
Asia-Pacific Cardiology Update 2014

2. University Sains Malaysia

Screening for Suitability of Stem Cell Treatment inHeart Failure secondary to Ischemic Cardiomyopathy:
A Multi-Center Experience
C.K.Choor1, H.H.Che Hassan1, M.R.Rafizi1, S.F.Mohamad1, M.Masliza1,S.P.Chin1, S.Fadilah1, O.Maskon1* This work was supported by the Ministry of Education grant
ERGS/1/2011/SKK /UKM/02/71

Screening for Suitability of Stem Cell Treatment in Heart Failure secondary toIschemic Cardiomyopathy: A Center Experience
C.K.Choor1, H.H.Che Hassan1, M.R.Rafizi1, S.F.Mohamad1, M.Masliza1, S.P.Chin1, S.Fadilah1, O.Maskon1
1 Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia
2 Beverly Wisshire Medical Center

Introduction : Despite the recent advances in medical and surgical treatments, heart failure resulting fromischemic cardiomyopathy remains the leading cause of cardiovascular mortality. We have embarked on a
study to examine if intracoronary transplantation of autologous mesencymal stem cell results in a clinicallyimportant improvement in left ventricular function in patients with ischemic cardiomyopathy.
Objectives : We aim to describe the patients that are screened in our center for the eligibility to be includedin the stem cell treatment.
Methodology : The inclusion criteria included male and female patients aged 40 to 80 years old with LVejection fraction <40%, excluding those with severe renal failure and previous CABG. Retrospective review
of echocardiogram done between 2011 and 2013 were undertaken.
Results : Of more than 1000 echocardiograms reviewed, there were 556 eligible patients. 287 patientsdetermined to have ischemic cardiomyopathy were screened, and the remaining with either non-ischemic
or indeterminate cause of poor ejection fraction were excluded. The mean age was 58.1 years with malegender predominant (83.2%). Mean ejection fraction was 31.3%. The traditional cardiac risk factors were
present with hypertension (63.8%), diabetes mellitus (53.3%) and dyslipidemia (29.3%) leading the way. A
total of 111 patients (38.7%) had a previous history of myocardial infarction. There were 54 (18.8%) ofpatients with severe chronic kidney disease (GFR < 30 ml/min). 85 patients (29.6%) underwent coronary
artery bypass grafting and 33 (11.5%) underwent coronary angioplasty. Excluding those with severe CKD andprevious CABG, leaving x(number) eligible for study inclusion.
Conclusions : Screening for eligible patients for the stem cell therapy utilising echocardiogram database hasidentified potential subjects to be recruited into the study screening phase.

Conclusions : Screening for eligible patients for the stem celltherapy utilising echocardiogram database has identified potential
subjects to be recruited into the study screening phase.

Stem Cell Therapy in Malaysia
3. unpublished“intra-coronary stem cells for post-infarct patients with
impaired left ventricular LV function”
Dr Soo Chee Siong, HSC Medical Center, Jalan Ampang, Kuala Lumpur, Malaysia

Several years ago
N = 30 cases

Methodology:
1.
2.
3.
4.

Revascularize the occluded vessel.
Pre-procedural proBNP and cardiac echocardiography.
Harvest stem cells from the patient’s own bone marrow.
Inject the harvested stem cells intra-coronary while theballoon is inflated in the target vessel.
5. Post-procedural proBNP and cardiac echo.

Stem Cell Therapy in Malaysia
Observations:
Success rate was about 50%. – similar to literature.
About 50% of the cases did extremely well
About 50% of the patients had no appreciable improvementin their LVEF on cardiac echo
But, no adverse effects were observed in them.

No cases of death from ventricular fibrillation.

Stem Cell Therapy in Malaysia
Observations:
The improvement in cardiac echo LVEF was modest:
Improvement by 5-10% - from 30% pre to 35-40% in mostcases
Improvement in proBNP levels was remarkable, consistent
with improvement in the patients symptoms.
e.g Many patients with minimal improvement in LVEF e.g. 30
to 35% but if the proBNP level normalize, they are generally
asymptomatic.
However, in those who had minimal improvement insymptoms, their proBNP levels remain elevated.

Stem Cell Therapy in Malaysia
Conclusions from Observations:
Success rate of 50% was in line with literature.
Possible Reasons for limited [50%] with no significant
improvement:
1. Patient’s own stem cells had different potencies
2. Using bone marrow stem cells rather than cardiacspecific stem cells
3. Inconsistency of the preparation of the stem cells bylaboratory.

Stem Cell Therapy in Malaysia
Final Conclusions:
Decided to stop doing intra-coronary stem cells for thetime being:

1. Limited success rate of 50%,
2. Uncertainty of the consistency/potency of the stem
cells prepared by stem cell provider,
3. Literature in this area does not seem to have mademuch progress in this area,

Stem Cell Therapy in Malaysia
Stem Cell Therapy in Cardiovascular Disease:
9 studies. ‘small’ studies.
3 presented at international meetings
1 unpublished6 publications in international journals

1Conclusions: MSC intracoronary infusion for patients with end-stage dilated
cardiomyopathy appears to be associated with symptomatic andechocardiographic improvement and lower mortality when compared toepidemiological data.
These results need to be validated in larger randomized trials

2Conclusions: Autologous bone marrow MSC treatment is safe and feasible fortreating chronic severe refractory DCM effectively via intracoronary or direct
intramyocardial administration at prescribed doses.

3Conclusions: Autologous bone marrow mesenchymal stem cells are safe forsevere dilated cardiomyopathy and appear to be beneficial, whether as
adjunctive treatment to revascularization in ischaemic cardiomyopathy or for
non-ischaemic dilated cardiomyopathy. The cell number required wereappropriate for respective mode of administration.
Larger randomized studies are now warranted.

4Conclusions: Rate-controlled freezing with 10% DMSO is a feasible and practicalmethod of cryopreserving MSC for cell storage and transportation without risk ofcell contamination or cell death.
Direct MSC injection may be beneficial as an adjunct to cardiac revascularization.

5Conclusions: The combination of BM-MNC and BM-MSC injection is better thanBM-MNC alone in promoting ulcer healing.
Larger studies involving larger samples are needed to confirm the findings.

6Conclusions: Our findings suggest that BMMSC infusion is efficacious in
reducing clinical disability as early 3 months with no adverse effects.
Autologous BMMSCs infusion appears safe and feasible in improving clinicaldisability in patients with acute MCA infarct.
Future trials involving larger samples are needed to confirm our findings.

Stem Cell Therapy in Malaysia
SUMMARY:
Stem Cell Therapy in Cardiovascular Disease:“early/preliminary” stages.
- Using BM Stem Cells

Number recruited were small.

Stem Cell Therapy in Malaysia
To Move Forward:
1. Funding
2. Institutions to take the lead, especially Universities.

3. Institutions should nominate “Champions”.

Stem Cell Therapy in Malaysia
3. Institutions should nominate “Champions”:
i. Ministry of Health – Institute of Medical Research.
ii. National Heart Institute IJN
Suhaini / Rosli / Jeswant / Chew / Aizai
iii. UMMC - Prof Wan Azman
iv. UKMMC - Prof Oteh
v. USM – Prof Zurkurnai
vi. UiTM – Prof Sazzlivii. UTM
viii. University Putra
ix. Universiti Sains Sarawaki. Universiti Sains Sabah
xi. University Monash Malaysiaxii. International Medical University

Thank You