1. Second Annual symposium, Chennai, India, 27Oct, 2007.PASRM 2007-006.
“Use of Bone Marrow derived Stem cells in Patients with Cardiovascular Disorders.”.

2. Fourth  Annual symposium, Chennai, India, 24Oct, 2009.PASRM 2009-007.
“Our experience with autologous bone marrow stem cell application in dilated cardiomyopathy”.

3. Fourth  Annual symposium, Chennai, India, 24Oct, 2009.PASRM 2009-008.
“Two sittings of Autologous Bone Marrow Stem Cells within two years in a case of Ischemic Cardiomyopathy”.

Use of Bone Marrow derived Stem Cells in Patients with Cardiovascular Disorders.
Madhu Sankar N (1), Karthik V(1), Rajesh V(1),  Prasad GN(1),  Kirtivasan V(1),  Naveen AT(2),    Abraham S(2,3),  Cherian KM(1).

1. Frontier Lifeline, Chennai, India
2. Nichi-In Centre for Regenerative Medicine, Chennai, India
3. Yamanashi University- Faculty of Medicine, Chuo, Japan

Patients with end stage heart failure have very few treatment options. The long waiting times for transplant and the complications associated with immunosuppression has led to the search for alternatives. Subsequent to the isolation and characterization of stem cells, tremendous advances have been made and the safety and feasibility of autologous bone marrow derived stem cells has been proven in preclinical studies. Clinical studies have also shown mobilized cells repair the infracted heart, improving function and survival. We have started a clinical study to evaluate the efficacy of bone marrow derived stem cells. Bone-marrow was aspirated from the right iliac crest and the stem cells were isolated by density gradient method and suspended according to the mode of delivery.

From Jan 2007 till date 10 patients (8 adults, 2 children, age) with end stage cardiovascular disorder of varied etiology (Ischemic left ventricular dysfunction - 6 patients, Primary pulmonary hypertension - 2 patients, Dilated cardiomyopathy -1 patient, Biventricular non-compaction -1 patient) underwent stem cell therapy. All patients were evaluated and cardiac function was measured by using echocardiography and thallium scintigraphy. There were no procedure related complications. These patients are being regularly followed-up and one patient who has completed 6-month follow-up has shown improvement in perfusion as well as increase in ejection fraction of 10%. Stem cell therapy in patients with end-stage cardiovascular disorder might be a promising tool by means of angiogenesis and other paracrine mechanisms.

Our experience with autologous bone marrow stem cell application in dilated cardiomyopathy
Mukund K(1), Keerthi N(1), Arjun K.Nambiar(1), Jayakrishnan AG (1), Senthil Nagarajan R(2), Murugan P(2), Manjunath S(2), Srinivasan V(2), Abraham S(2,3)

1. Omega Hospiatal, Mangalore, India
2. Nichi-In Centre for Regenerative Medicine, Chennai, India
3. Yamanashi University- Faculty of Medicine, Chuo, Japan

Background: Use of autologous bone marrow stem cell is a newly evolving treatment modality for end stage cardiac failure as reported in the literature. We report our experience with two patients with dilated cardiomyopathy who underwent this treatment after failure of maximal conventional therapy.

Method: A 29 year old Male patient with history of orthopnea and PND, with a diagnosis of dilated cardiomyopathy and echocardiographic evidence of severe LV dysfunction was referred for further treatment. His echo on admission showed EF of 17% and no other abnormal findings except elevated bilirubin levels. He was in NYHA functional class IV. He received intracoronary injection of autologous bone marrow stem cells in January 2009. 254X10⁶ cells were injected with a CD34+ of 0.20%. His clinical condition stabilized and he was discharged home. He received a second injection of 22X10⁶ in vitro expanded stem cells with a CD34+ of 0.72% in Aug 2009. He is now in NYHA class II-III with EF 24%.

A 31year old Male patient with history of increasing shortness of breath, severe over the past 3-4 days was admitted for evaluation and treatment. His echo on admission showed EF of 20% and was in NYHA functional class IV. Coronary angiogram was normal and he was stabilized on maximal anti failure measures. He received intracoronary autologous bone marrow stem cell injection of 56X10⁶ with a CD34+ of 0.53% in August 2009. His clinical condition stabilized over the next 10 days and he was discharged home.

Conclusion: In our experience of two cases of dilated cardiomyopathy, safety of intracoronary injection of autologous bone marrow stem cells both isolated and in vitro expanded has been proven in both the cases with efficacy proven in one of the cases. Long term follow-up of these two cases and inclusion of more number of similar cases where all available conventional therapies have not resulted in significant improvement for such studies are planned.

Two sittings of Autologous Bone Marrow Stem Cells within two years in a case of Ischemic Cardiomyopathy.
Rao YY(1), Bakthavathsalam G(1), Manjunath S(2), Ruban Rex P(2), Senthil Nagarajan R(2), Baskar S(2), Abraham S(2,3)

1. KG Hospital, Coimbatore, India
2. Nichi-In Centre for Regenerative Medicine, Chennai, India.
3. Yamanashi University- Faculty of Medicine, Chuo, Japan.

Background: A 66yrs  old  Diabetic and  Hypertensive female, who had  Anterior  Wall  MI 5yrs  ago  and had undergone  PTCA  with  Stent  to  LAD,  was  admitted for  refractory  CHF with  Severe  LVD  2yrs  ago  and the LVEF then was  25%. Coronary Angiogram was done which showed Total Occlusion of LAD and 50% Stenosis of RCA.

Method: 100ml of her bone marrow was harvested from posterior iliac crest and the BMMNCs were isolated as per cGMP protocols at NCRM, Chennai and 325X10⁶ cells with a CD34+ count of 0.84% were injected the next day by transfemoral catheter into the coronary arteries.  Post treatment she had clinical improvement.  EF increased by 5%.  She was in Class-II for 1 year. After 1 yr, she was admitted with severe  CHF  and  EF  had deteriorated to  20%.
This time BMMNCs isolated from the bone marrow were subjected to in vitro expansion by which the initial 0.15% CD34+ cells increased by nearly 30 fold to 4.62%. Totally 315X10⁶s cells were injected into the coronaries. Post treatment there is clinical  as  well  as Echo evidence of improvement  and  BNP level  has  come  down  by  30%.

Conclusion: Isolated and expanded CD34+ cells from bone marrow mononuclear cells of autologous origin, administered into the coronaries in an Ischemic Cardiomyopathy  patient has been proven to be safe. The clinical and  Echo  cardiographic  improvement  that  has sustained for long-term, proves the feasibility and efficacy of two consecutive autologous bone marrow stem cell applications, one isolated and the second ex vivo expanded. More case studies may be undertaken to further evaluate the results.