Bone Marrow-derived Cells' Contribution to Tumor Formation and Epithelial Cells Regeneration in the Gastrointestinal Tract
Recent experimental studies showed that circulating bone marrow-derived stem cells
contribute to the formation of cancers cells. However, it is not clear whether this is
applicable to human beings or not. In addition, bone marrow-derived cells are considered to
play a significant role in regeneration of inflamed epithelial cells of the gastrointestinal
tract during graft versus host disease (GVHD), which sometimes occurs after bone marrow
transplantation (BMT). On the other hand, it is well known that the incidence of solid
tumors is significantly increased following bone marrow transplantation.
One purpose of this study is to determine the role of bone marrow-derived cells in the tumor
formation and acute or chronic inflammation of the gastrointestinal tract in human beings,
and the other is to discover early cancers of the gastrointestinal tract in the subjects
received BMT by conducting surveillance for detecting second tumor, periodically.
All subjects are the patients received allogeneic BMT in Tokyo Metropolitan Komagome
Hospital for hematopoietic disorders.
For determining the role of bone marrow-derived cells in the solid tumors and inflammation
like GVHD, suitable candidates are females who received allogeneic BMT from male donors,
because the most reliable marker of bone marrow-derived cells is identification of the Y
chromosomes from the male donor in the tissue of female.
For the early detection of gastrointestinal cancers, the subjects are confined to patients
without recurrence of original disorder at least 1 year after BMT. They are scheduled to
undergo a medical inspection using gastrointestinal endoscopy, periodically.
When tumor or any other lesions are discovered, biopsy specimens are taken and proceed to
pathological examination. According to the results, the patients will have proper
The tissue specimens from the tumors or inflammation in female recipients from male donors
are processed for Y fluorescent in situ hybridization (FISH) analysis and
immunocytochemistry using monoclonal antibodies such as cytokeratin, CD45 and so on.
First of all, informed consent to this study should be gained from the subjects.
Study 1: to determine the role of bone marrow-derived cells on inflammation such as GVHD
1. Subjects are female recipients from male donors.
2. When they have some symptoms suggesting acute or chronic GVHD, gastrointestinal
endoscopy is conducted and biopsy specimens are taken from the lesions for the definite
diagnosis and identification of bone marrow-derived cells.
3. Pathological investigation(Y-FISH etc.) is conducted using the tissue specimens.
Study 2: to conduct surveillance for second malignancy and to determine the role of bone
marrow-derived cells on the formation of the tumor
1. Subjects are confined to bone marrow recipients without the recurrence of the original
disorder at least 1 year after BMT.
2. A medical inspection for gastrointestinal tract is performed using periodical
3. The tissue from tumors or any other lesions discovered are taken as biopsy specimen
and processed for pathological examination. Regarding the female recipients from male
donors, the same procedure as in the study 1 is taken for pathological study.
Observational Model: Cohort, Time Perspective: Prospective
Naoto Egawa, MD
Japan: Institutional Review Board