Umbilical Cord Stem Cells

Abstract & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: Issues related to cost, quality control, and the need for ethnic diversity in public banks preclude the universal collection of units from all obstetric deliveries. Directed donation of cord blood should be considered when there is a specific diagnosis of a disease within a family known to be amenable to stem cell transplantation.

Source: Moise K. Umbilical Cord Stem Cells. Obstet Gynecol. 2005; 106:1393-1407.

In the December Green Journal there was an excellent review by Ken Moise on the current status of umbilical cord blood stem cells. Since this is a topic patients frequently ask about, this month I will depart from the usual alert format to abstract this informative article.

Presently more than 5 million peripheral blood samples from potential bone marrow donors are being stored under the auspices of the National Marrow Donor Program. These libraried samples have been "typed" by compulsive and comprehensive HLA antigen testing. Currently, more than 70 hematopoietic, autoimmune, metabolic, and oncologic disorders lend themselves to treatment with bone marrow stem cells from donors registered in this ambitious and successful program.

Treatment consists of first ablating the affected recipient’s bone marrow to give a fresh start to a unit of implanted hematopoietic stem cells capable of developing into normal mature blood cells. Success of the method is based on how long it takes for the patient to obtain adequate concentrations of neutrophils, platelets, and erythrocytes in the his/her peripheral blood (the recovery time).

There are some drawbacks to this type of therapy. Not every potential recipient will have a HLA matching donor in the system. For example, 12% of Caucasians, 20% of Hispanics, 22% of Asians, and 41% of African Americans were unmatchable as of 2003 figures. Also, as of 2003 the average time taken to find a match was about 53 days and then another 4-6 weeks have been required to find the donor, evaluate his or her suitability and to schedule a bone marrow aspiration.

Another problem is the unfortunate tendency in some cases for graft-vs-host (GVH) reactions in which transplanted T-lymphocytes, found among the progenitor cells earmarked for therapy, attack the tissue of the recipient. Interestingly, the T-lymphocytes may also have a beneficial effect by attacking residual malignant cells in the recipient’s system (graft-vs-leukemic effect—GVL).

Umbilical cord blood contains hematopoietic stem cells that have some advantages over bone marrow cells. These stem cells appear be more robust, replicating better in in vitro settings. Also, there is less GVH activity and they survive better if the HLA match is not perfect. Surprisingly, these cells have the same GVL capacity.

Other advantages involve the logistics of the process. For example, banked cord blood samples are all "typed" and ready to go when needed, which only translates into an average 2-week lag time. Also it is a painless process, avoiding the discomfort of a donor marrow aspiration.

The greatest disadvantage is that the cord blood yields fewer stem cells per unit, simply because of the limited volume of blood that can be aspirated from the umbilical cord after birth. This results in longer recovery times for new blood cells to appear in the recipient’s circulation (7 days longer then neutrophils, 30 days longer for platelets).

Presently there are 22 public cord blood banks participating in the National Marrow Donor Program that are processing samples across the United States. These centers operate under very strict guidelines and the samples have been collected compulsively under strict aseptic conditions.

Since there are more advantages then disadvantages of cord blood stem cells, this may well be the way of the future for some hematopoietic diseases. Now there is evidence that totipotential fetal mesenchymal cells from cord blood could be used for tissue transplantation, thereby opening up the potential of treatment for Parkinson’s disease, spinal cord injury, and myocardial infarction, among many other conditions.

Commentary

Fetal stem cell therapy is not only an extremely exciting area but also a highly polarized one—certainly regarding embryonic stem cells. However, a common issue that confronts clinicians today emanates from a spin off potential benefit from cord blood banking- autologous transplants. This is a concept that also has appealed to entrepreneurs. Twenty four private cord banks have sprung up offering biologic insurance for infants against possible conditions to come. Storing these cord bloods comes at a cost to the parents of about $1100-$1700 for initial processing and an additional cost of about $120 a year for storage. Since these bloods are earmarked for possible use only by their owners, HLA typing is not being done.

Interestingly, one company advertises that currently 1 out of 27 infants would benefit from their cord bloods and, with future progress in stem cell therapy, 1 out of 2 could possibly use their banked samples. With this type of hype it would seem uncaring for parents not to make this investment in their child’s future. However, many genetic mutations are already in stem cells, rendering these autologous cells unsuitable for treating many types of conditions, including leukemia. Also, most importantly, current objective assessments indicate that the real chance of needing one’s own stem cells is about 1 in 2,700, although this figure could improve somewhat if use of mesenchymal cells from the umbilical cord pans out. Also, other problems include incomplete knowledge about the lifespan or even usefulness of stem cells stored for more then 15 years, the legal aspects of ownership, or, frankly, how long these presently unregulated companies will survive.

For the above reasons, the American College of Obstetrics and Gynecology, the American Academy of Pediatrics, and the Royal College of Obstetricians and Gynecologists have not recommended this pathway for parents. In fact, in Italy these types of commercial banks are interdicted by law.

Here in the United States, patients obviously are free to choose this option, but at least when asked, we can give them objective advice regarding its advantages and disadvantages.

References

  1. Moise K, Umbilical Cord Stem Cells. Obstet Gynecol. 2005;106:1393-1407.
  2. Gluckman E, et al. Human leukocyte antigen matching in cord blood transplantation. Semin Hematol. 2005;42:85-90.
  3. Bieback K, et al. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004; 22:625-634.
  4. Sugarman J, et al. Optimization of informed consent for umbilical cord blood banking. Am J Obstet Gynecol. 2002; 187:1642-1646.
  5. Ballen KK, et al. Bigger is better: maternal and neonatal predictors of hematopoietic potential of umbilical cord blood units. Bone Marrow Transplant. 2001;27:7-14.
  6. American College of Obstetricians and Gynecologists. Routine storage of umbilical cord blood for potential future transplantation. ACOG Committee Opinion 183. Washington, DC: ACOG; 1997.
  7. Cord blood banking for potential future transplantation: subject review. American Academy of Pediatrics. Work group on Cord Blood Banking. Pediatrics. 1999;104:116-118.
  8. Royal College of Obstetricians and Gynaecologists Scientific Advisory Committee. Umbilical cord blood banking. Opinion paper 2. Available at: www.rcog.org.uk/index.asp?PageID=545. Accessed January 19, 2006.