Umbilical cord blood stem cells

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When cord blood is called stem cells derived from umbilical cord blood or placenta remaining blood is collected after the umbilical cord of the child.

It has been known since the late 1980s that umbilical cord blood is rich in stem cells that are able to restore the blood-forming system. The reason for this is the migration of blood formation , which is located in the liver and spleen during fetal development , to the bone marrow . This migration takes place in the last trimester of pregnancy via the child's bloodstream . This means that at the time of birth there is an unusually large number of stem cells in the child's blood and thus also in the remaining blood of the umbilical cord and placenta.

Cord blood stem cells were first used medically in 1988 by the French doctor Eliane Gluckman in Paris to treat a child with Fanconi anemia . By 2011, umbilical cord blood stem cells had been used more than 20,000 times, mainly as third-party transplants (→ stem cell transplantation ), and over 600,000 donations were stored. NetCord alone reported 10,434 transplants.

properties

Advantages of cord blood stem cells over stem cells from bone marrow :

• to win with little risk
• Stocking of stem cell preparations for ethnic minorities and children of mixed ethnic origin
• low contamination with latent viruses and tumor cells
• immediate availability through long-term storage ( cryopreservation )
• better tolerance if the HLA characteristics of the donor and recipient do not match
• simple provision when needed instead of laborious coordination between the bone marrow collection center and the transplant center
• high growth potential of stem cells
• high differentiation potential of the stem cells
• lower risk of acquired chromosomal changes and mutations

The ability of umbilical cord blood stem cells to develop not only into blood cells but also into nerve , liver , blood vessel , muscle , bone , cartilage and islet cells has already been proven . This property is used in biotechnology to regenerate body tissue. However, this has not yet been used on humans.

Current studies also show that umbilical cord blood cells are well suited for reprogramming into induced pluripotent stem cells . Compared to the adult cells previously used for reprogramming, for example from the skin , they have the advantage that they do not show any age-related genetic or epigenetic changes and no loss of telomerase activities.

Disadvantages of cord blood stem cells compared to stem cells from bone marrow:

• limited quantity
• only to be won at the birth of a child
• prolonged aplasia of blood formation compared to bone marrow stem cells

It is also criticized that the donation ties up unnecessary human resources in the maternity clinics. Clamping the umbilical cord early to donate umbilical cord blood contradicts current standards and leads to a decrease in the amount of blood in children.

Gene defects that z. B. can lead to leukemia or type I diabetes mellitus are also present in the umbilical cord blood.

Application of umbilical cord blood

Treatment of children and adults

The disadvantage of cord blood transplantation compared to bone marrow stem cells is the lower amount of stem cells that are available. Treatment of adult patients is only possible with a sufficient number of cells. Stem cell transplants currently recommend a minimum cell dose between 10 and 30 million nucleated cells (MNC) per kilogram of body weight of the recipient if the donor and recipient are not identical ( allogeneic transplantation ). If the recommended cell dose for the treatment of adults is not achieved, the simultaneous transplantation of two umbilical cord blood preparations can be an alternative.

However, given the benefits of cord blood such as better tolerance and immediate availability, cord blood transplantation is also gaining importance in adults. For example, cord blood is currently used in 20% of all stem cell transplants in the USA; in Japan, the cord blood quota for children and adults is already 50% combined.

Allogeneic transplantation (foreign transplantation)

The allogeneic transplantation of umbilical cord blood is currently the norm. Umbilical cord blood stem cells are transferred to the patient, which do not come from himself, but from a suitable donor. If the donation is not a directed donation, cord blood stem cells from stem cell registries are used. Allogeneic cord blood stem cells are currently used primarily for leukemia , haematopoietic disorders and genetic diseases. Just over a third of all allogeneic transplanted cord blood was used in adults.

Autologous transplant (own transplant)

So far, around 130 cases of the body's own (autologous) cord blood transplants are known. The first application of autologous cord blood stem cells was in 1999 in a child with a neuroblastoma in Brazil. In addition to tumor diseases such as neuroblastoma or retinoblastoma, cases of bone marrow failure ( aplastic anemia ), type 1 diabetes and early childhood brain damage have also been treated with umbilical cord blood , according to autologous cord blood banks .

In 2009, at the University Clinic in Bochum, cerebral palsy in a 2.5-year-old boy was successfully treated for the first time with the body's own umbilical cord blood.

Side effects

In 2011, a study followed 104 patients after a stem cell transplant from umbilical cord blood. Around 10% developed a chronic colon inflammation that was detectable in the tissue, often with granulomatous inflammation.

Conservation of umbilical cord blood

As a donation to a stem cell registry

The donation to a stem cell registry is used to set up a pool of stem cell preparations that oncologists and hematologists can access if necessary. By cryopreservation it is also possible to stock stem cells for patients with relatively rare occurring genetic endowment or of mixed ethnicity, and to shorten the donor search in the application.

The donation is free of charge for the parents, as the costs are covered by donations (e.g. from the José Carreras Foundation ) and transfer fees paid by the patient's health insurance.

In Germany, umbilical cord blood can be donated to the stem cell registers in Düsseldorf, Mannheim, Munich , Freiburg, Erlangen, Dresden and Hanover. These registers work with around 75 hospitals in numerous German cities. Collection is currently only possible in those cooperating clinics. In Switzerland, there are clinics in Basel, Bern, Geneva, Liestal and Lugano for cord blood donation.

As a (directed) donation to treat a sick family member

Stem cells from a close relative, preferably a sibling, are well suited for transplantation if the tissue compatibility is matched. For this purpose, if the disease is already present, the umbilical cord blood is collected and processed specifically for later treatment of the patient. After evaluating around 500 umbilical cord blood transplants among HLA- identical siblings, Eurocord comes to the conclusion that the procedure shows good results.

The (directed) umbilical cord blood donation is free of charge for parents and is offered by the stem cell registries as well as private umbilical cord blood banks. This means that umbilical cord blood donation is possible across the board for family members.

As self-preservation for private provision

The self-preservation of umbilical cord blood (autologous storage) for private prevention is a controversial issue: The main point of criticism is that the probability of using one's own stem cells in childhood is very low. In addition, in the case of hematological diseases in the child, it must be checked whether the stem cells already contain the disposition to develop the disease. In its 1999 guideline , the German Medical Association still considers the use of umbilical cord blood to treat illnesses in adults to be speculative. Clear criticism has also come from the chairman of the German Society for Hematology and Oncology, Gerhard Ehninger , who considers the commercial freezing of umbilical cord blood to be "profiteering".

However, since the umbilical cord blood also contains pluripotent and proliferative stem cells, there is reason to hope that in the future it will be possible to use them to grow special tissues or cell clusters for the treatment of serious diseases or to develop new stem cell-based forms of treatment. In mid-August 2012, the National Institutes of Health , USA , had already registered over a dozen studies with one's own umbilical cord blood. One focus is the treatment of children with cerebral palsy and other early childhood brain damage. Since 2005, patients have been treated with their own umbilical cord blood at Duke University, Durham, USA. In 2012, a South Korean pilot study with 20 patients came to the conclusion that transfusing one's own umbilical cord blood in cerebral palsy is feasible and safe. However, the neurological improvements in children with diplegia and hemiplegia are significantly higher than in those with tetraplegia . In addition, the international Juvenile Diabetes Research Foundation has started a study on the treatment of type 1 diabetes mellitus in cooperation with the University of Florida, Gainesville, USA . According to initial assessments, therapy with one's own umbilical cord blood could help maintain insulin production in the patient's body. Overall, these therapies are in the very early experimental stage with an uncertain outcome.

The parents have to pay for the self-preservation of umbilical cord blood. The costs in Germany are around 1200 to 2500 euros for the first twenty years of storage. So far, only a few cases are known in which the costs have been partially reimbursed by health insurance companies. Self-preservation is largely possible nationwide in Germany.

There are only very few providers in Germany who allow private storage. The two largest include Vita34 based in Leipzig and eticur based in Munich. Eticur works together with the stem cell bank at the University Hospital Erlangen , and Vita34 has been the first private stem cell bank in Europe since 1997. With a storage time of 25 years, both are priced at 2,600 to 2,700 euros.

As a donation for stem cell research

In umbilical cord blood donation for research, stem cells are used to examine their mode of action and to develop new stem cell-based therapies for the treatment of diseases.

The donation for stem cell research is offered by the stem cell registers, university institutions and private umbilical cord blood banks. It is free for parents, but not possible across the board.

A donation cannot be made if the mother has received blood products in the weeks leading up to the birth. This also includes anti-D prophylaxis in the event of Rhesus incompatibility .

Long term storage of stem cells

Studies have shown that cord blood stem cells last for over 20 years without losing their vitality and ability to proliferate. According to the Fraunhofer Institute for Biomedical Technology , stem cells can theoretically be stored for several centuries without losing any of their potential.

The reason for this is that the life processes inside the cell come to a complete standstill at temperatures below −130 ° C. Theoretically, the stem cells can be kept indefinitely. "The only limitation of the storage period is due to the cosmic radiation , which also hits the cell samples in the frozen state and in the steel tank".

literature

• Verena Reimann, Ursula Creutzig, Gesine Kögler: Stem cells from umbilical cord blood in transplant and regenerative medicine . In: Deutsches Ärzteblatt , Volume 106, No. 50, 2009, pp. 831–836 (review article; online ).

Individual evidence

1. ^ Eliane Gluckman, Annalisa Ruggeri, Fernanda Volt, Renato Cunha, Karim Boudjedir, Vanderson Rocha: Milestones in umbilical cord blood transplantation. In: British Journal of Hematology. 154, 2011, p. 441, doi : 10.1111 / j.1365-2141.2011.08598.x .
2. ↑ Netcord: NetCord History ( English ) 2014. Accessed on May 16, 2014.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.  
3. ↑ Bone Marrow Transplantation 2001, 27: 1-6)
4. ↑ ^{a b} Haase et al. doi : 10.1016 / j.stem.2009.08.021
5. ↑ Alessandra Giorgetti, Nuria Montserrat a. a .: Generation of Induced Pluripotent Stem Cells from Human Cord Blood Using OCT4 and SOX2. In: Cell Stem Cell. 5, 2009, p. 353, doi : 10.1016 / j.stem.2009.09.008 .
6. ↑ L. C Edozien: NHS maternity units should not encourage commercial banking of umbilical cord blood. In: BMJ. 333, 2006, p. 801, doi : 10.1136 / bmj.38950.628519.68 .
7. ↑ Eileen K. Hutton, Eman S. Hassan: Late vs Early Clamping of the Umbilical Cord in Full-term Neonates. In: JAMA. 297, 2007, pp. 1241-1252, doi : 10.1001 / jama.297.11.1241 .
8. ↑ Human Immunology 2006, 67: 398-404
9. ↑ Parent's Guide to Cord Blood Foundation: Children who used their own cord blood ( English ) Archived from the original on September 30, 2009. Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved October 8, 2009. 
10. ↑ Bone Marrow Transplant. 1999, 24 (9): 1041
11. ^ Press release 151 of the Ruhr University Bochum from May 21, 2013
12. ↑ AF Herrera, G. Soriano, AM Bellizzi, JL Hornick, VT Ho, KK Ballen, LR Baden, CS Cutler, JH Antin, RJ Soiffer, FM Marty: Cord colitis syndrome in cord-blood stem-cell transplantation. In: The New England Journal of Medicine . Volume 365, Number 9, September 2011, pp. 815-824, doi : 10.1056 / NEJMoa1104959 , PMID 21879899 .
13. ↑ List of DKMS extraction clinics ( Memento of the original from May 11, 2013 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. 
14. ↑ Swiss Blood Stem Cell Foundation: Where can you donate umbilical cord blood?
15. ^ E. Gluckman, A. Ruggeri, V. Rocha, E. Baudoux, M. Boo, J. Kurtzberg, K. Welte, C. Navarrete, SM van Walraven: Family-directed umbilical cord blood banking. In: Haematologica. Volume 96, number 11, November 2011, pp. 1700-1707, doi : 10.3324 / haematol.2011.047050 , PMID 21750089 , PMC 3208689 (free full text) (review).
16. ↑ Statement of the German Working Group for Bone Marrow and Blood Stem Cell Transplantation ( Memento of the original from July 11, 2013 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
17. ↑ BMBF brochure on umbilical cord blood ( Memento of the original dated May 24, 2006 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
18. ↑ NIH: Studies with search of: autologous cord blood ( English ) 2012. Accessed August 7, 2012.
19. ↑ pediatrics.duke.edu: Study Amazing Recovery Attributed to Cord Blood ( Memento of the original from March 5, 2011 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (October 2, 2008) 
20. ↑ Lee et al. Journal of Translational Medicine 2012, 10:58
21. ↑ jdrf.org: Study Name: Transfusion of Autologous Umbilical Cord Blood to Reverse Hyperglycemia in Children with Type 1 Diabetes  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (October 2, 2008)  
22. ↑ Parent's Guide to Cord Blood Foundation: Tables of Private Bank Features & Pricing ( English ) Archived from the original on March 28, 2009. Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved March 24, 2009. 
23. ↑ Umbilical Cord Blood Supplier.de. Umbilical cord blood supplier.de editors, accessed on February 6, 2020 . 
24. ^ German bone marrow donor file: DKMS umbilical cord blood bank . Retrieved March 9, 2012.
25. ^ German bone marrow donor file: List of cooperating clinics . Retrieved on March 9, 2012.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.  
26. ↑ Broxmeyer, HE et al .: Hematopoietic stem / progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood. Blood. 2011 May 5; 117 (18): 4773-7.