Cell-intrinsic factors governing quiescence vis-à-vis activation of adult hematopoietic stem cells.

Hematopoiesis is a highly complex process, regulated by both intrinsic and extrinsic factors. Often, these two regulatory arms work in tandem to maintain the steady-state condition of hematopoiesis. However, at times, certain intrinsic attributes of hematopoietic stem cells (HSCs) override the external stimuli and dominate the outcome.

Pharmacological Inhibition of p38 MAPK Rejuvenates Bone Marrow Derived-Mesenchymal Stromal Cells and Boosts their Hematopoietic Stem Cell-Supportive Ability.

The therapeutic value of mesenchymal stromal cells (MSCs) for various regenerative medicine applications, including hematopoietic stem cell transplantations (HSCT), has been well-established. Owing to their small numbers in vivo, it becomes necessary to expand them in vitro, which leads to a gradual loss of their regenerative capacity. Stress-induced mitogen-activated protein kinase p38 (p38 MAPK) signaling has been shown to compromise the MSC functions.

Cryopreservation of mesenchymal stromal cell-derived extracellular vesicles using trehalose maintains their ability to expand hematopoietic stem cells in vitro.

The multitude of clinical trials using mesenchymal stromal cells (MSCs) has underscored their significance as a promising cell source for regenerative therapies. Most studies have however shown that MSCs get entrapped into the microvasculature of lungs, liver and spleen. In addition to intercellular communication, MSCs exert their effects in a paracrine manner by secretion of extracellular vesicles (EVs).

Mesenchymal stromal cell-derived extracellular vesicles as cell-free biologics for the ex vivo expansion of hematopoietic stem cells.

Hematopoietic stem cell transplantation (HSCT) is the ultimate choice of treatment for patients with hematological diseases and cancer. The success of HSCT is critically dependent on the number and engraftment efficiency of the transplanted donor hematopoietic stem cells (HSCs). Various studies show that bone marrow-derived mesenchymal stromal cells (MSCs) support hematopoiesis and also promote ex vivo expansion of HSCs.