Patient-Specific Embryonic Stem Cells Derived From Human SCNT Blastocysts

Abstract

Numerous diseases and injuries result from defects in a single cell type and, if the defective cells could be replaced with appropriate stem cells, progenitor cells, or cells differentiated in vitro, effective treatment at the cellular level might be possible. If human embryonic stem cells (hESCs) can be generated from human nuclear transfer (NT) blastocysts in which the somatic cell nucleus comes from the individual patient, the nuclear genome will be identical to that of the NT donor. This could prevent immune rejection. The investigators have established 11 hESC lines by NT of skin cells from patients having a disease or injury into donated oocytes. The cell lines were derived from somatic cells of male or female patients who were 2 to 56 years of age and had spinal cord injury, juvenile diabetes, or congenital hypogammaglobulinemia. DNA fingerprinting using human short tandem repeat probes showed that each cell line almost certainly originated from the respective patient donor rather than resulting from enucleation failure and subsequent parthenogenetic activation. The cell lines were grown on human feeders from the same NT donor or from genetically unrelated persons. They were established at high rates regardless of the sex or age of the NT donor. The stem cells were pluripotent and chromosomally normal, and in each instance, they matched the NT patient’s DNA. Immunologic compatibility was demonstrated by showing that each subject’s major histocompatibility complex was identical with that of the corresponding NT-hFSC. Nine of the 11 stem cell lines were derived from single menstrual cycles. It seems clear that stem cell lines can be generated from somatic cells of patients with disease or injury. Cell transplantation treatments might be advanced by using patient-specific NT-hESCs grown without animal cell co-culture. This approach also holds promise of clarifying human developmental processes and of disclosing the causes of many complex diseases.