1. Umbilical Cord Blood: An Alternate Source of Stem Cells Susan Parker Advisor: David Fahringer PA-C University of Kentucky College of Health Sciences Physician Assistant Program

3. Objectives w Understand the process of stem cell transplants w Discuss methods of retrieval of stem cells w Learn benefits and disadvantages of using umbilical cord stem cells w Discuss ethical concerns surrounding umbilical cord blood use

4. Stem Cell Transplants w Stem cell transplants are indicated for hematopoietic malignancies, bone marrow failure syndromes, and genetic immunodifiecient disorders. w When a patient needs a stem cell transplant, a suitable donor must be found. w Immune ablation, to reduce GVHD risk, is administered under intense medical supervision in a sterile environment. w The patient’s recovery begins with an extremely weak and vulnerable immune system with a wide range of complications and opportunistic infection risk.

5. Stem Cell Transplants (cont’d) w 6 human leukocyte antigens (HLAs) need to be matched between donor and recipient to improve post-transplant prognosis w Only 30% of patients will have the ideal situation: related donor with all six HLA matches w If no suitable related donor, the process of searching the National Marrow Donor Program (NMDP) begins. w Currently, there are two sources of stem cells available to patients, bone marrow derived and umbilical cord derived stem cells.

6. Your Chances of Finding a Donor w 10 million registered BM donors worldwide w Caucasion has a 50% chance of finding a donor w Minorities are lower, donor programs targeting subpopulations to increase diversity of donor pool. w Basically, <50% chance of finding a donor under any circumstance.

7. Bone Marrow Stem Cells w Standard stem cell source for over 40 years w Obtained by bone marrow aspiration of the pelvis of donor w Relatively no risk to donor other than pain (no anesthetics used) w From beginning search to actual transplant takes 3-5 months

8. Umbilical Cord Stem Cells w First successful transplant in 1988 w Relatively low risk to mother and baby w Beginning search to transplant in as few as 21 days

9. Umbilical Cord Collection w Collected after delivery of baby, before delivery of placenta w Contraindicated in moderate-high risk births w Collected under aseptic techniques and stored at -80  F

10. Umbilical Cord Retrieval

11. Benefits of UCSC over BMSC w Decreased transplant time w No chance of donor having acquired disease, infection, nor the possibility of donor declining procedure w Increased diversity of donor pool, much higher rates of minority donation w UCSC have acceptable mortality rates with 4/6 HLA matches w Faster neutrophil engraftment (lower chance of engraftment) w Best prognoses seen in pediatric patients w Non-myeloblative immune destruction has better outcome with UCSC transplant

12. Drawbacks of UCSC w Longer time to immune system recovery due to immaturity of cells w Leads to increased GVHD and infection risk (but diseases less severe than with BM) w Less effective for adults w Cell dose of one sample usually inadequate for patients with increased body mass w Possible unknown genetic conditions of newborn donor

13. The Bottom Line w Chance of engraftment similar between BM and UC w Decreased severity of complications with UC w Pooling of two or more UC samples has promising results, ex-vivo expansion of cells being researched w Collecting cord blood has variable results due to technique and delivery complications w Best outcome is still with 6/6 HLA matched related bone marrow donor w UC contains mesenchymal stem cells that have shown promise in becoming various types of tissues: neural, cardiac, hepatic, renal, etc.

14. Ethics of Using UCSC w Alturistic donation – no cost to donor, increased attention to minorities, LOTS of paperwork and stipulations w Private donation - $1500 + $150/month with no guarantee of successful collection or storage w Recommendations for families with known genetic and inherited disorders w Pressure on families during an already stressful life event w Targeting middle and upper class mothers and obstetricians in wealthy areas w Not available to all women in all areas

15. Private Cord Banking: Advertisement w http://www.cryo-cell.com/video_center/angelvision/index.asp http://www.cryo-cell.com/video_center/angelvision/index.asp

16. References w Armson, 2005, B. Umbilical Cord Banking: Implications for Perinatal Providers. J Obstet Gynaecol Can. 2005 March; 27(3):263-90. w Ballen, 2005, K. New trends in umbilical cord blood transplantation. Blood. 2005 May; 105(10): 3786-91 w Barker, 2003, J., Weisdorf, D., et al. Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood. 2003 September; 102(5): 1915-19. w Bieback, 2004, K., Kern, S., Kluter, H., Eichler, H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004; 22: 625-634. w Fisk, 2005, N., Roberts, I., Markwald, R., Mironov, V. Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified? PloS Medicine. 2005 February; 2(2): 44- 47. w Laughlin, 2005, M., Giralt, S., Spitzer, T. Umbilical Cord Blood Transplantation: A New Alternative Option. Hematology. 2005; 377-383. w Lu, L., Yang, S., et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with Hematopoiesis-supportive function and other potentials. The Hematology Journ. 2006; 91(8):1017-26. w O’Brien, 2006, T., Tiedemann, K., Vowels, M. No longer a biological waste product: umbilical cord blood. MJA. 2006 April; 184(8): 407-410. w Tuch, 2006, B. Stem Cells: A Clinical Update. Family Physician. 2006; 35: 719-721. w Wang, 2005, F., Huang, X., Zhang, Y., Chen, Y., Lu, D. Successful transplantation of double unit umbilical-cord blood from unrelated donors in high risk leukemia with a long follow-up. Chinese Medical Journal. 2005; 188(9): 772-6.