How Do You Mend a Broken Heart?

Stem cell research opening the door to cardiac recovery

One day in a laboratory in the Punjab University, Dr. Sanjiv Dhingra asked his wife and fellow PhD candidate if she was available for lunch. She couldn’t go because she was busy observing some algae. So, no lunch date with his beloved. Instead, he laid the groundwork that led to the “a-ha” moment that has shaped his career.

“I think this can only come with innovation; to me innovation is very important.”

Dr. Dhingra was curious about his wife’s algae and took some of it back to his own lab.

“We were inducing experimental atherosclerosis in our rats at that time,” says Dr. Dhingra, Principal Investigator, Cardiac Regeneration and Tissue Engineering Laboratory, Institute of Cardiovascular Sciences, St. Boniface Hospital. “I injected extract from that algae in rats at different time points. You’ll be surprised to know that it decreased cholesterol levels significantly. Nobody had known about that previously. I thought if I went into research, I can do these kinds of things throughout my life.”

That thrill of discovery coupled with the potential to help people opened Dr. Dhingra’s eyes and he decided to pursue medical research. Heart failure patients of the not-too-distant future will be glad he did.

Dr. Dhingra and his colleagues have been working with ethical stem cells to create a patch – like a bandage – that would be applied after a heart attack. At the core of this work is a very special relationship with a university in Rome, Italy. Dr. Dhingra directs the Canada/Italy Tissue Engineering Laboratory (CITEL) in collaboration with Università degli Studi di Roma Tor Vergata, an Italian university.

Perfect cells

In essence, this international team is making tissue. In the St. Boniface Hospital Research Centre lab, Dr. Dhingra and his team are figuring out how to prevent the tissue from being rejected in the heart after transplantation. The implications of a successful result are enormous.

“When there is a heart attack, heart cells start dying due to lack of oxygen and blood supply,” he explains. “Unfortunately once heart cells die, they don’t multiply like other cells in the body do. This is the real problem. So whatever loss happens due to cell death, it leads to permanent damage and ultimately to heart failure.”

Dr. Dhingra and company are trying to create “perfect cells” so they can’t be rejected by the host immune system. That’s the goal – and it begins with understanding why rejection happens in the first place. What are the mechanisms behind rejection?

“I strongly believe that if we’re able to understand those mechanisms, we can prolong survival of transplanted stem cells in the heart,” he says.

Preventing rejection

What they have learned so far is that when they transplant stem cells in the damaged heart, the behaviour of some of the genes in the transplanted cells is no longer regulated, due to a lack of oxygen.

“We have shown that if we’re able to maintain the function of those genes, cell survival increases,” explains Dr. Dhingra. “We do this by genetic manipulation or by pharmacological means.” They are now seeking ways to enhance the positive effects of these interventions and have the genes function for longer periods of time.

The work is captivating and would have sounded strange just a few decades ago. A goal that seemed impossible not that long ago, now seems within reach with a little more testing, technology, collaboration, and, above all, innovation.

Only with innovation

The goal is “to replace all dead cells after a heart attack with healthy cardiac cells derived from ethical stem cells to preserve heart function and prevent heart failure,” he says. “I think this can only come with innovation; to me innovation is very important.”

Dr. Dhingra also believes that St. Boniface Hospital is the right place to get the job done.

“I’m a basic scientist. I want to take my findings to the patients,” he says. “At St. Boniface, I can work closely with clinicians and collaborate with them. This is a big plus, so that is why I believe this is the right place for me.”

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