Umbilical Cord Blood and Transplantation

Göbek kordonu ana ile bebek arasında kan, gaz ve bunlara bağlı biyolojik materyallerin geçişini
sağlayan biyolojik bir aracıdır. Kordon kanı bankaları ülkemizde son 15 yılda kamu iştirakleri ve özel
sektör aracılıyla çoğalmıştır. Ülkemizdeki bu tıbbi gelişimleri hukuki olarak da desteklenmesi ve uygun
zemin sağlanması gerekmektedir. Bu çalışma kordon kanının saklanması ve bertaraf edilmesi sürecinin
hukuki alandaki durumu ortaya koymaya ve eksiklikleri tespit etmeyi hedeflemektedir.
5 Temmuz 2005 tarihli Kordon Kanı Bankacılığı Yönetmeliği uygun şekilde ve miktarda elde edilmiş olan
kordon kanının saklanmasına ilişkin hususları düzenlemiş ve herhangi bir sebeple bertaraf edilmesi
hakkında 20 Mayıs 1993 tarihli Tıbbi Atıkların Kontrolü Yönetmeliğine ve dolayısıyla bu yönetmeliği ilga
ederek yerine yürürlüğe giren 25 Ocak 2017 tarihli aynı isimli yönetmeliğe atıf yapmıştır. Kordon kanı
yapısı itibariyle uygun şartlarda saklanmaması halinde Tıbbi Atıkların Kontrolü Yönetmeliğince
enfeksiyon yapıcı tıbbi atık olarak nitelendirilmektedir. Herhangi bir şekilde çevre, insan ve belediye
veya ambalaj atığı ile aynı ortamda olması, bunlara karışması yasaklanmış olan enfeksiyon yapıcı tıbbi
atığın ise lisanslanmış tıbbi atık işleme tesisinde bertaraf edilmesi gereklidir. Toplanmış olan kordon
kanının niteliği veya niceliğinden yahut kontamine ya da enfekte olmasından kaynaklı bertaraf halleri
ayrıksı tutulduğunda saklanacak veya saklanmakta olan kanın bertaraf edilmesine karar vermeye kim
yetkilidir: kan sahibi mi, banka ile saklama sözleşmesi akdeden mi, çocuk adına çocuğun velisi/velileri
mi? Eldesi güç ve kök hücre bakımından zengin olan kordon kanının, kök hücre ihtiyacı olan birçok
hastanın tedavisine umut ışığı olması yerine bertaraf edilmesi ne kadar adaletli olacaktır?
Bu çalışma ile allojenik ve otolog olarak saklanan kordon kanının mülkiyeti ve çocuğun üstün yararı ve
üstün kamusal menfaat ilkeleri doğrultusunda kanın anonimleştirilmesi veya bertaraf edilmesi hususu
irdelenmeye çalışılacaktır.
Anahtar Kelimeler: Kordon kanı, Hak sahipliği, Bertaraf, Çocuğun üstün menfaati, Kamu yararı,
Allojenik saklama

Following intraparenchymal injection of the dopamine (DA) neurotoxin 6-hydroxydopamine, we previously demonstrated passage of fluoresceinisothiocyanate labeled albumin (FITC-LA) from blood into the substantia nigra (SN) and striatum suggesting damage to the blood-brain barrier (BBB). The factors contributing to the BBB leakage could have included neuroinflammation, loss of DA neuron control of barrier function, or a combination of both. In order to determine which factor(s) was responsible, we assessed BBB integrity using the FITC-LA technique in wild-type (WT), tumor necrosis factor alpha (TNF-α) knockout (KO), and minocycline (an inhibitor of microglia activation) treated mice 72 hrs following treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with WT mice, TNF-α KO mice treated with MPTP, showed reduced FITC-LA leakage, decreased numbers of activated microglia, and reduced pro-inflammatory cytokines (TNF-α and interleukin 1β) associated with significant MPTP-induced DA neuron loss. In contrast, minocycline treated animals did not exhibit significant MPTP-induced DA neuron loss although their FITC-LA leakage, numbers of activated microglia, and MPTP-induced cytokines were markedly attenuated. Since both TNF-α KO and minocycline treatment attenuated MPTP-induced BBB dysfunction, microglial activation, and cytokine increases, but had differential effects on DA neuron loss, it appears that neuroinflammation and not DA neuron loss was responsible for disrupting the blood-brain barrier integrity.

Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and allows early interventions to improve engraftment and outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34+ cells, with 19F-containing PLGA nanoparticles which were detectable with both flow cytometry and magnetic resonance spectroscopy (MRS). In addition, labeled CD34+ cells maintain their capacity to proliferate and differentiate, which is pivotal for successful engraftment after transplantation in vivo. These results set the stage for in vivo tracking experiments, through which the homing efficiency of transplanted cells can be studied.

Most patients who require a sibling stem cell transplantation do not have a matched donor. In our experience, only 1/3 patients have a matched unrelated donor (MUD); therefore, the majority of the patients will require umbilical cord blood (UCB). Patients treated for hematologic diseases with UCB transplants were included. UCB selection and conditioning regimens were performed according to the Minnesota group. Graft-versus-host disease (GVHD) prophylaxis, infection prevention, and patient care were performed according to institutional guidelines. We analyzed patients and graft demography, neutrophil and platelet recovery, chimerism kinetics, GVHD incidence, overall (OS), progression-free survival (PFS) and transplant-related mortality (TRM). We included 29 patients with a median age of 34.8 years (range 15-55). Eighteen were male and the median weight was 72.6 kg (range 54-100). Nineteen patients had acute leukemia. Myeloablative (MA) conditioning was used in 27 patients. Seventeen received double UCB (DUCB) grafts. Median total nucleated cell (10(7)/kg) was 4.2 (range 3.9-4.9) and 4.4 (range 2.8-6.3) for single UCB (SUCB) and DUCB transplants, respectively. Median time for neutrophil engraftment was 24.7 (range 14-43) and 25.8 days (range 14-52) after SUCB and DUCB transplants, respectively. Median time for platelet engraftment was 147 (range 30-516) and 81 days (range 37-200) after SUCB and DUCB transplants, respectively. All the patients receiving MA conditioning had >95% chimerism shortly after transplant. Cumulative incidence of grades II-IV and III-IV acute GVHD was 41% and 20%, respectively. Localized chronic GVHD was seen in 14% of the patients. Median follow-up was 16.7 months (range 1-63). Five-year OS and PFS were 38% and 39%, respectively. One-year TRM was 42%. UCB transplantation is associated with potential cure of hematologic malignancies and our results are similar to other series. Studies are needed to decrease mortality and improve immune reconstitution.