Activated HoxB4-induced hematopoietic stem cells from murine pluripotent stem cells via long-term programming.

Hematopoietic stem cells (HSCs) are multipotent cells that form the entire blood system and have the potential to cure several pathogenic conditions directly or indirectly arising from defects within the HSC compartment. Pluripotent stem cells (PSCs) or induced pluripotent stem cells (iPSCs) can give rise to all embryonic cell types; however, efficient in vitro differentiation of HSCs from PSCs remains challenging. HoxB4 is a key regulator orchestrating the differentiation of PSCs into all cells types across the mesodermal lineage, including HSCs. Moreover, the ectopic expression of HoxB4 enhances the in vitro generation and expansion of HSCs. However, several aspects of HoxB4 biology including its regulatory functions are not fully understood. Here, we describe the role of HoxB4 in indirectly inhibiting the emergence of mature CD45+ HSCs from iPSCs in vitro. Forced activation of HoxB4 permitted long-term maintenance of functional hematopoietic stem and progenitor cells (HSPCs), which efficiently reconstituted hematopoiesis upon transplantation. Our method enables an easy and scalable in vitro platform for the generation of HSCs from iPSCs, which will ultimately lead to a better understanding of HSC biology and facilitate preparation of the roadma for producing an unrestricted supply of HSCs for several curative therapies.

Physiological characteristics of the body fluid in lymphedematous patients postbreast cancer surgery, focusing on the intracellular/extracellular fluid ratio of the upper limb.

AIM: The aim of this research was to determine the physiological characteristics of patients with lymphedema following breast cancer surgery, based on differences between the quantity of body water in the right and left fingertips, with a view to establishing whether or not this simple measurement could serve as a predictive index for the onset of lymphedema. METHOD: The research was conducted at a hospital in Hiroshima, Japan (August 2004 to December 2004). Observations were made on 39 female breast cancer patients who had undergone surgery and 45 healthy female participants. Additional information was collected via interviews with the individual participants. The quantity of body water in all the participants was measured by using a bioimpedance spectrum analysis system. Comparisons of the intracellular/extracellular fluid ratios (I/Es) were made between the edema patients and the non-edema patients, with further testing being done between the affected and unaffected sides of the upper limb in the edema patients. RESULTS: In the edema patients, significant differences were recognized between the affected side's upper limb I/E and the unaffected side's upper limb I/E. In relation to the affected side's upper limb I/E of the edema patients, even when the mean value and standard deviation were included, the value did not exceed 1.0 and the mean - 3 SD value of the affected side's upper limb I/E in the non-edema patients was 1.04. CONCLUSIONS: The results suggest that measurements of the affected and unaffected sides' upper limb I/E showed a potential for use as a reliable predictive index for lymphedema.