PMID- 17041717
OWN - NLM
STAT- MEDLINE
DCOM- 20061204
LR  - 20180604
IS  - 1537-744X (Electronic)
IS  - 2356-6140 (Print)
IS  - 1537-744X (Linking)
VI  - 6
DP  - 2006 Oct 9
TI  - Infusion of autologous retrodifferentiated stem cells into patients with 
      beta-thalassemia.
PG  - 1278-97
AB  - Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin 
      chain of the adult hemoglobin gene. This results in excess accumulation of 
      unpaired alpha-chain gene products leading to reduced red blood cell life span 
      and the development of severe anemia. Current treatment of this disease involves 
      regular blood transfusion and adjunct chelation therapy to lower blood 
      transfusion-induced iron overload. Fetal hemoglobin switching agents have been 
      proposed to treat genetic blood disorders, such as sickle cell anemia and 
      beta-thalassemia, in an effort to compensate for the dysfunctional form of the 
      beta-globin chain in adult hemoglobin. The rationale behind this approach is to 
      pair the excess normal alpha-globin chain with the alternative fetal gamma-chain 
      to promote red blood cell survival and ameliorate the anemia. Reprogramming of 
      differentiation in intact, mature, adult white blood cells in response to 
      inclusion of monoclonal antibody CR3/43 has been described. This form of 
      retrograde development has been termed "retrodifferentiation", with the ability 
      to re-express a variety of stem cell markers in a heterogeneous population of 
      white blood cells. This form of reprogramming, or reontogeny, to a more 
      pluripotent stem cell state ought to recapitulate early hematopoiesis and 
      facilitate expression of a fetal and/or adult program of hemoglobin synthesis or 
      regeneration on infusion and subsequent redifferentiation. Herein, the outcome of 
      infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients with 
      beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC 
      subjected to hematopoietic-conducive conditions into patients with 
      beta-thalassemia reduced mean blood transfusion requirement, increased mean fetal 
      hemoglobin synthesis, and significantly lowered mean serum ferritin. This was 
      always accompanied by an increase in mean corpuscular volume (MCV), mean 
      corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration 
      (MCHC) in such patients. No adverse side effects in response to the infusion of 
      autologous RSC were noted. This novel clinical procedure may profoundly modify 
      the devastating course of many genetic disorders in an autologous setting, thus 
      paving the way to harnessing pluripotency from differentiated cells to regenerate 
      transiently an otherwise genetically degenerate tissue such as thalassemic blood.
FAU - Abuljadayel, Ilham Saleh
AU  - Abuljadayel IS
AD  - TriStem U.K. Limited. iabuljadayel@tristemcorp.com
FAU - Quereshi, Huma
AU  - Quereshi H
FAU - Ahsan, Tasnim
AU  - Ahsan T
FAU - Rizvi, Shakil
AU  - Rizvi S
FAU - Ahmed, Tamseela
AU  - Ahmed T
FAU - Khan, Sabiha Mirza
AU  - Khan SM
FAU - Akhtar, Jawaid
AU  - Akhtar J
FAU - Dhoot, Ghazi
AU  - Dhoot G
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061009
PL  - United States
TA  - ScientificWorldJournal
JT  - TheScientificWorldJournal
JID - 101131163
RN  - 0 (Hemoglobins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Adult Stem Cells/*physiology/*transplantation
MH  - Blood Transfusion
MH  - Cell Differentiation
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Hematopoiesis
MH  - Hemoglobins/biosynthesis
MH  - Humans
MH  - Male
MH  - Stem Cell Transplantation/adverse effects/methods
MH  - Transplantation, Autologous
MH  - Treatment Outcome
MH  - beta-Thalassemia/*therapy
PMC - PMC5917317
EDAT- 2006/10/17 09:00
MHDA- 2006/12/09 09:00
PMCR- 2006/10/09
CRDT- 2006/10/17 09:00
PHST- 2006/10/17 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/10/17 09:00 [entrez]
PHST- 2006/10/09 00:00 [pmc-release]
AID - 205405 [pii]
AID - 10.1100/tsw.2006.229 [doi]
PST - epublish
SO  - ScientificWorldJournal. 2006 Oct 9;6:1278-97. doi: 10.1100/tsw.2006.229.