The Stem Cells of the Spleen: New Basic Research Findings from Our LabIn 2003, our lab identified a new stem cell in the spleen of mice that could increase the speed of pancreas regeneration
once the underlying autoimmune disease was removed. Knowledge about the function of this splenic stem cell has
expanded in the last seven years. Other research groups have shown that this splenic stem cell: 1) can be expanded fromanimal samples in the lab to form sheets of insulin secreting islets (1); 2) can regenerate the islets of animals with type 2
diabetes (2); and 3) can contribute to the regeneration of bone, heart, cranial nerves and salivary glands in animals (3, 4,5, 6).
With this information in hand, we wanted to know: what is the full regenerative potential of the splenic stem cells? Thatis, can we predict all of the possible tissues that these cells could help heal through regeneration?
To answer this question, we collaborated with other scientists at Harvard to examine the proteins found in splenic stem
cells, which would give us information on the types of tissues these cells could possibly become. We also compared thesplenic stem cells to certain closely related cancer cells, since research has shown that some stem cells (i.e. embryonicstem cells) can turn cancerous. Our findings were recently published in the International Journal of Biochemistry & Cell
Biology (6).
Based on their protein expression profile, we found that human splenic stem cells appear to have the capacity to change
into a wide number of different tissue types, much in the same way that embryonic stem cells and induced pluripotent
stem cells (iPS cells, cells that are reprogrammed into an earlier state with embryonic qualities and these iPS cells canform whole new mice). In addition to finding the proteins we expected to see based on what we knew from animalstudies (e.g. proteins associated with development of pancreas, bone, cranial nerves/central nervous system, heart, andblood tissue), we also saw that human splenic stem cells had proteins characteristic of the developing eye, testes,thymus, kidney, liver, lung, placenta, gut, tongue, and skin. In addition, our protein analysis suggests that splenic stem
cells have a low likelihood of transforming into cancerous cells.
Our new work also asked another question? What happens in the spleen of an untreated autoimmune NOD mouse withactive diabetic disease? Are there signs of splenic stem cells contributing to the healing process? Using some of the newstem cell proteins we identified in this study, we demonstrate the splenic stem cells are proliferating and also expressing
more of the fetal proteins. Like other recent data on the splenic stem cells in cardiac repair, it is likely the expansion ofstem cells in the mouse spleen is a healing response for pancreas repair.
What does this all mean? Because the splenic stem cells appear to have the capacity to become many different cell types,
they have potential to be used in a wide range of applications, such as organ regeneration, new disease therapies, ordisease prevention. This is exciting for future research in regenerative medicine. In terms of type 1 diabetes, while wehope that all people with longstanding autoimmunity will have their immune disease removed and insulin-secreting cells
regenerate on their own in our BCG human trials, we also think it is important to have safe adult stem cells available incase the pancreas of long term diabetics does not kick in to regenerate on its own.
References:
1. Robertson SA, Rowan-Hull AM, Johnson PR. The spleen--a potential source of new islets for transplantation? J Pediatr
Surg. 2008 Feb;43(2):274-8.
2. Yin D, Tao J, Lee DD, et al. Recovery of islet beta-cell function in streptozotocin- induced diabetic mice: an indirect rolefor the spleen. Diabetes. 2006 Dec;55(12):3256-63.
3. Macias MP, Fitzpatrick LA, Brenneise I, McGarry MP, Lee JJ, Lee NA. Expression of IL-5 alters bone metabolism andinduces ossification of the spleen in transgenic mice. J Clin Invest. 2001 Apr;107(8):949-59.
4. Swirski FK, Nahrendorf M, Etzrodt M, et al. Identification of splenic reservoir monocytes and their deployment to
inflammatory sites. Science. 2009 Jul 31;325(5940):612-6.
5. Lonyai A, Kodama S, Burger D, Davis M, Faustman DL. The promise of Hox11+ stem cells of the spleen for treating
autoimmune diseases. Horm Metab Res. 2008 Feb;40(2):137-46.
6. Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo M, et al. Identification of Splenic Reservoir
Monocytes and Their Deployment to Inflammatory Sites. Science (2009) 325:612 – 616.
7. Dieguez-Acuña F, Kodama S, Okubo Y, Paz AC, Gygi SP, Faustman DL. Proteomics identifies multipotent and low
oncogenic risk stem cells of the spleen. Int J Biochem Cell Biol. 2009 Dec 18. [Epub ahead of print].