• Stem Cell Therapies

  • Jacob Hanna Interview

Interview with Jacob Hanna MD, PhD

Currently, the only potential cure available for sickle cell anemia is bone marrow or cord blood transplantation. Cord blood and bone marrow contain adult stem cells. Since donor adult stem cells from the bone marrow or cord blood have the ability to create functional red blood cells, transplants can essentially cure sickle cell patients. However, a major drawback to this cure is that finding a proper donor match is very difficult and thus rare. Therefore, bone marrow or cord blood transplantation is not, nor will it ever be, a cure for all patients with sickle cell anemia.

Induced-pluripotent cells (iPS cells) are pluripotent stem cells derived from somatic cells, such as skin cells. Pluripotent stem cells have the ability to differentiate into 220 different cell types in the human body, including bone marrow cells. Unlike human embryonic pluripotent stem cell whose extraction destroys the developing embryo, iPS cells are derived from adult somatic cells and therefore are non-controversial. Finally and most importantly, since iPS cells are derived from the patient him or herself, donor matching is not necessary. Therefore, iPS cell therapy could be a full-proof and thorough cure for all sickle cell patients in the near future. Dr. Jacob Hanna, a leader in the field of iPS cell therapy at the MIT Whitehead Institute in Boston predicts that iPS cell therapy may be deemed safe as a cure for sickle cell anemia in humans within the next several years.

In 2007, Hanna and colleagues at the Whitehead Institute cured sickle cell in mice with induced pluripotent stem cell therapy. The group extracted skin cells from the tails of mice with sickle cell anemia and de-differentiated them to an earlier state of development which was pluripotent in nature. The researchers then replaced the mutated gene that causes sickle cell anemia in the extracted cells with a healthy gene. Once the iPS cells had differentiated into bone marrow cells, the researchers reintroduced them into the mice. Amazingly, the mice began to produce healthy blood cells, effectively curing their sickle cell anemia.

I interviewed Dr. Hanna in 2010 about his research with induced pluripotent stem cells. Please read the highlights of the interview specifically related to sickle cell anemia below. If you would like to view the interview in full, which includes background information about Dr. Hanna, his plans to help unite Palestinian and Israeli scientists, other diseases iPS cells may be able to cure, and his future research, click here to download a PDF file of the transcript. The audio version is also available online.

Arjun Prabhu: In 2007, you were the lead author on the breakthrough study which proved that induced pluripotent stem cell therapy can cure sickle cell anemia in mice. What made you first begin to work with induced pluripotent stem cell? Why did you choose sickle cell anemia as the target disease and why mice as your model? Sorry, multiple questions!

Jacob Hanna: So, when I joined the lab in 2007, just half a year after a major breakthrough of Yamanaka making these iPS cells. Of course this opened tens of questions which five years later now, we barely know the answers for. So this was a very obvious thing to want to work with iPS cells. Choosing the sickle cell anemia model, this is a disease that is relevant, it is very abundant. The genetic mutation is known, so we know what we want to correct. And it is a blood disease, so we can transplant stem cells to the bone marrow. It is very hard to replace a brain, right, but it easy to replace the bone marrow. So the combination of these factors led us to take this as a target.

AP: Why did you decide to choose mice as your model, I guess that is a pretty common choice.

JH: [We wanted to] have a kind of full in vivo experiment in the animal. Obviously we can’t do this with humans because we still don’t know the safety of the cells and working with pigs or monkeys would be much harder. Being able to do all these manipulations in mice makes it a very good, easy-to-handle experiment.

AP: What are some of the advantages then to using induced pluripotent stem cell therapy as a cure for sickle cell anemia over some other publicized treatments such as adult stem cells from [donor] bone marrow or cord blood cells?

JH: The first advantage of iPS cells is the comfort of being customized, meaning you will make cells that are genetically identical from the donors. We don’t have to look for matching donors and that is the major issue in transplantation therapy. The fact that we can reprogram a skin biopsy from a patient and make pluripotent cells, and these stem cells are identical to him is major, there is no other way to do this.

AP: So essentially if you were able to do this [treatment] in humans, you could cure every single [sickle cell anemia patient] using his own cells, is this true?

JH: There are limitations, yes we can make stem cells from every patient, but we still have a way to go in the sense that we don’t have a lot of good protocols for differentiation, to make different types of neurons for example to make insulin-producing cells. So there is a lot of work on how to differentiate stem cells in a controlled and reproducible manner. So this is something we will continue to work on in the field, but I believe that in many cases our knowledge is advancing in such a rapid pace that we will be at least [able to say] “this can be done in humans.”

AP: Right, so I know this is kind of a tough question to answer because like you said science and research [on stem cells] is moving so quickly but do you have any sort of estimate for when you think induced pluripotent stem cells might be able to be used as a pretty common therapy for sickle cell anemia in humans?

JH: That’s a really tough one. I think blood diseases are likely to be the first candidates as I said because we have a way to deliver cells to the bone marrow because of the nature of this organ, we can do this. I want to be optimistic and say five years.

AP: For people who want to help but aren’t really interested in science, is there anything they can do to help?

JH: First of all, we are really thankful for any moral support for people who are trying to do this despite a lot of difficulties. Second, I think for patients, [if they can] really be cooperative in [research] studies, or by providing samples through hospitals and organized programs, this is a very meaningful way that families can really do their share to boost research. That way we can learn from sometimes their painful experiences but at the same time it will enable us to do this research and alleviate many of these syndromes. For many families, this is a very meaningful way to support research.