The Chromatin Remodeling Complex CHD1 Regulates the Primitive State of Mesenchymal Stromal Cells to Control Their Stem Cell Supporting Activity.

The primitive state (stemness) of mesenchymal stromal cells (MSCs) is responsible for supporting the function of tissue-specific stem cells to regenerate damaged tissues. However, molecular mechanisms regulating the stemness of MSCs remain unknown. In this study, we found that the primitive state of MSCs is hierarchically regulated by the expression levels of the chromatin remodeling complex, CHD1, with CHD1 expression levels higher in the undifferentiated state, and decreasing upon MSC differentiation.

Reconstituting Human Cutaneous Regeneration in Humanized Mice under Endothelial Cell Therapy.

Much of our understanding of human biology and the function of mammalian cells in tissue regeneration have been derived from mechanistically and genetically manipulated rodent models. However, current models examining epidermal wound repair fail to address both the cross-species mechanistic and immunogenic differences simultaneously. Herein, we describe a multifaceted approach intended to better recapitulate human skin recovery in rodent models.

Ectopic vascularized bone formation by human umbilical cord-derived mesenchymal stromal cells expressing bone morphogenetic factor-2 and endothelial cells.

Mesenchymal stromal cells (MSCs) isolated from numerous tissues including human fetal tissue are currently used in cell therapy and regenerative medicine. Among fetal tissues, the umbilical cord (UC) is one of the sources for both MSCs and endothelial cells (ECs). To establish ectopic vascularized bone tissue formation, UC-derived MSCs and ECs were isolated.

Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem cells: a model of molecular convergence for stemness.

The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells (HSCs) without overriding the normal stem cell pool size. A similar enhancement of HSC self-renewal occurs when signal transducer and activator of transcription 3 (STAT3) is activated in HSCs. In this study, to gain insight into the functional organization of individual transcription factors (TFs) that have similar effects on HSCs, we investigated the molecular interplay between HoxB4 and STAT3 in the regulation of HSC self-renewal.

Efficient bone marrow transduction by gene transfer with allogeneic umbilical cord blood serum and plasma: an implication for clinical trials.

Low in vivo transduction efficiency and safety concerns have been hurdles for effective hematopoietic stem cell (HSC) gene therapy. Here, we investigate whether the safety and efficiency of retroviral gene transfer into HSCs can be improved by using human allogeneic umbilical cord blood (UCB)-derived supplements instead of fetal bovine serum (FBS). When CD34(+) cells were cultured ex vivo in UCB-derived serum (CBS) or plasma (CBP), comparable or higher maintenance of HSCs was observed than in FBS and serum-free substitution medium (SFM) as assessed by the frequency of positive engraftment and the level of engraftment in NOD/SCID mice after transplantation of cultured cells.

A novel function of interleukin-10 promoting self-renewal of hematopoietic stem cells.

Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting ability, but the factors regulating the process remain poorly understood. Here, we show that Interleukin-10 (IL-10), a pleiotropic immune modulating cytokine, can also play a role in regulating HSC self-renewal. First, a quantitative decrease of primitive hematopoietic cell populations, but not more matured cells, was observed in the bone marrows of IL-10 disrupted mice as determined by long-term in vitro cultures or in vivo competitive repopulation assays.