Maternal transplantation of human umbilical cord blood cells provides prenatal therapy in Sanfilippo type B mouse model.
Numerous data support passage of maternal cells into the fetus during pregnancy in both human and animal models. However, functional benefits of maternal microchimerism in utero are unknown. The current study attempted to take advantage of this route for prenatal delivery of alpha-N-acetylglucosaminidase (Naglu) enzyme into the enzyme-deficient mouse model of Sanfilippo syndrome type B (MPS III B). Enzymatically sufficient mononuclear cells from human umbilical cord blood (MNC hUCB) were intravenously administered into heterozygote females modeling MPS III B on the 5th day of pregnancy during blastocyst implantation. The major findings were 1) administered MNC hUCB cells transmigrated and diffused into the embryos (E12.5); 2) some transmigrated cells expressed CD34 and CD117 antigens; 3) transmigrated cells were found in both the maternal and embryonic parts of placentas; 4) transmigrated cells corrected Naglu enzyme activity in all embryos; 5) administered MNC hUCB cells were extensively distributed in the organs and the blood of heterozygote mothers at one week after transplantation. Results indicate that prenatal delivery of Naglu enzyme by MNC hUCB cell administration into mothers of enzyme-deficient embryos is possible and may present a significant opportunity for new biotechnologies to treat many inherited disorders.
Garbuzova-Davis
Svitlana
S
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida, College of Medicine, Tampa, FL 33612, USA. sgarbuzo@hsc.usf.edu
Gografe
Sylvia J
SJ
Sanberg
Cyndy Davis
CD
Willing
Alison E
AE
Saporta
Samuel
S
Cameron
Don F
DF
Desjarlais
Tammy
T
Daily
Jennifer
J
Kuzmin-Nichols
Nicole
N
Chamizo
Wilfredo
W
Klasko
Stephen K
SK
Sanberg
Paul R
PR
D000118:Acetylglucosaminidase / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D019070:Cell Lineage; D002465:Cell Movement; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D046128:Fetal Therapies / Q000379:methods; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000637:transplantation*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009084:Mucopolysaccharidosis III / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D010920:Placenta / Q000648:ultrastructure; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D019009:Proto-Oncogene Proteins c-kit; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase