When I was young, my father tried to teach me to eat everything put on my plate (though it was an uphill battle, since I was quite the finicky child). One of the few “bizarre” foods that I took a liking to, though, was sucking the marrow out of goat, lamb, or beef curries (my father was clearly not a devout Hindu). Even now, it’s one of my favorite parts of such dishes, and I recently added San Diego to my travel wish list if just to eat swordfish marrow (thanks for the tip, Andrew Zimmern).
But that’s clearly not what we’re going to talk about right now. Everyone knows that human bone marrow is rich in stem cells, specifically hematopoietic. In fact, without research on bone marrow, stem cells might not be as well understood, and accordingly we might not have reached the current burgeoning development in the cell therapy field. Last time in our Amazing Samples blog series, we discussed the value of adipose tissue cells. This time, let’s savor the rich history of bone marrow research.
… Man, I should cook some curry.
Today, even children taking early biology classes learn that bone marrow’s primary function is to produce blood, and that description is quickly being expanded to include other produced cell types (from mesenchymal stem cells). It’s only been in the past century that science has developed to the point of understanding such things, and just in time – while recently-discovered nuclear radiation was shown to kill cancer cells, the required levels also inflicted lethal damage on the healthy bone marrow of those exposed. Two doctors pioneered the technique of transplanting the bone marrow, replacing the damaged tissue with healthy hematopoietic cells from a donor.
The first bone marrow transplantation is credited to Dr. Donnall Thomas, who in the late 1950’s ended up curing a patient of acute lymphocytic leukemia by following the radiotherapy with a bone marrow transplant from the patient’s twin (called syngeneic). Shortly thereafter Dr. George Mathé in France performed the first non-twin bone marrow transplants, showing that allogeneic transplants were possible with the proper technique – good news for everyone who didn’t have a twin.
Today, a number of techniques can be used to help to replenish a chemotherapy or radiotherapy patient’s bone marrow after treatment. If the patient’s bone marrow is relatively free of cancer cells, they can prepare an autologous transplantation – procuring the patient’s own marrow and cryopreserving it until the patient is ready for a transplant. Should the patient’s marrow not be appropriate for re-transplantation, then a compatible donor must be found for an allogeneic implant. In fact, past the benefit of replacing the damaged marrow, healthy marrow can even help fight against certain cancers while in remission, with the graft-generated immune cells actively attacking the damaged cancer cells, and it is being investigated for a number of autoimmune indications as well. See the NCI’s Stem Cell Fact Sheet for more information, and if you’re willing to donate your bone marrow or related cells to help someone with their cancer treatment, here are a few different organizations, depending on your location:
- The US Health Resources and Services Administration specifically names the C.W. Bill Young Cell Transplantation Program, aka Be The Match Registry, as the national registry.
- DKMS, or Delete Blood Cancer, also operates in the UK, Germany, Poland, and Spain.
Why Kill What You Can Convert?
In surprising research just published last week, it turns out that exposing malignant marrow cells to a certain agonist antibody not only transforms them back into benign cells, but specifically into natural killer (NK) cells that singularly target still-malignant cells. Cancer research has been looking for techniques to do the first step – after all, converting cancer cells back into healthy tissue would eliminate many of the traditional dangers and collateral damage from chemotherapy (such as the damaging of bone marrow).
Richard Lerner et al at the Scripps Institute have been researching cell transformation for a few years, and just two years ago had already discovered that healthy bone marrow stem cells could be transformed—transdifferentiated—into a brain progenitor cell, with but a single protein. They were expanding their research when they discovered that not only could this single antibody convert leukemia cells into healthy tissue without affecting healthy marrow cells, but a certain number of them turned into high-specificity NK cells that only attack their malignant former brethren. While obviously this single facet of the discovery only shows the antibody’s value against leukemia, imagine the possibilities if it were shown to have a similar effect on other types of cancer.
Bone Marrow on a Chip
I’m not talking about a bizarre snack food. The use of microfluidic devices, or organ-on-a-chip technology, is a bioengineering trend to enable higher efficiency and throughput in research at lower costs, and just last year Harvard’s Wyss Institute for Biologically Inspired Engineering managed to accurately reproduce bone marrow in this form. The marrow-on-a-chip even maintains function similar to in vivo marrow, with stem cells in similar proportions for up to 1 week.
This greatly increases the viability of any research of bone marrow responses to new therapies, as well as the general research into the stem cells found inside. See the Wyss Institute’s video for more information!
Even if marrow isn't the most popular food for all people, its scientific value is undeniable. Whether spearheading transplant medicine or being used for new applications in oncology, bone marrow cells are an Amazing Sample.
To learn more about the important variables to consider if you have a cell-based therapy in development and the unique logistical challenges associated with autologous cell therapies, please download our eBook Cell Therapy Logistics: Beyond the Basics