A novel autologous stem cell procedure for the treatment of aplastic anaemia using reprogrammed mature adult cells: a pilot study.

Background & objectives: Aplastic anaemia is a life threatening rare bone marrow failure disorder. The underlying haematopoietic cellular deficit leads to haemorrhage, infection and severe anaemia. The treatment of choice for this haematological condition is allogeneic bone marrow transplantation from fully matched HLA sibling. Though this procedure is curative in the majority of young patients with aplastic anaemia, extending this benefit to older patients or those lacking a family donor remains a major challenge. Herein, the safety and efficacy of infusing autologous retrodifferentiated haematopoietic stem cells (RHSC) into four patients with aplastic anaemia without the use of any pre- or post-conditioning regimen including immunosuppression is described. Methods: Un-mobilized, mononuclear cells were harvested from four patients with acquired aplastic anaemia by aphaeresis. Mononuclear cells of patients were cultured with purified monoclonal antibody against the monomorphic regions of the beta chain of MHC class II antigens (Clone CR3/43) for 3 h, to obtain autologous RHSC. Autologous RHSC were washed and infused into the four patients without the use of any pre- or post-conditioning regimen. Thereafter, the efficacy (engraftment) of autologous RHSC was assessed in these patients. Results: Following single infusion of the autologous RHSC, two of the four patients with aplastic anaemia become transfusion independent for more than seven years. Karyotyping and G-banding analysis prior and post-procedure in all patients remained the same. Interpretation & conclusions: The findings of this pilot study demonstrated the functional utility of reprogrammed fully differentiated adult cells into pluripotent stem cells with extensive repopulation potentials in a human setting and without any pre- or post-conditioning regimen, including immunosuppression. This autologous approach of stem cell creation may broaden the curative potentials of stem cell therapy to a wider population of patients with aplastic anaemia, including many patients suffering from other haematological and non-haematological disorders.

Gagtric Adenocarcinoma with Choriocarcinomatous and Hepatoid Differentiation: Report of a case

Association of the hepatoid and choriocarcinomatous components in adenocarcinoma of the stomach is extremely unusual and raises a possibility of new approach understand the histogenesis of gastric hepatoid adenocarcinoma. This paper describes a Borrmann type III adenocarcinoma of the stomach with both choriocarcinomatous and hepatoid components in composite tumor pattern in a 50-year-old man. Tubular arrangement of differentiated embryonalcarcinoma was encountered in choricarcinomatous and hepatoid areas, which showed strong immunoreactivity to beta-HCG and AFP, respectively. The findings suggest that gastric adenocarcinoma may have a potential of differentiation toward embryonal carcinoma. from which both choriocarcinoma and hepatoid variant of gastric adenocarcinoma may develop by retrodifferentiation.