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in the bone marrow
Two new studies have revealed elements that are key to hematopoietic stem and progenitor cell (HSPC) mobilization.
In one study, investigators discovered that elevated levels of the peptide hormone angiotensin II increases HSPC mobilization in the context of vasculopathy and sickle cell disease (SCD).
In the other study, researchers found that p62, an autophagy regulator and signal organizer, is required to maintain HSPC retention in the bone marrow.
Jose Cancelas, MD, PhD, of the University of Cincinnati College of Medicine in Ohio, is the corresponding author on both studies.
In the first paper, published in Nature Communications, Dr Cancelas and his colleagues noted that patients with vasculopathies have an increase in circulating HSPCs.
“This phenomenon may represent a stress response contributing to vascular damage repair,” he said. “So the question becomes, how can we learn from these patients?”
Using mouse models of vasculopathy and vasculopathy-associated SCD, Dr Cancelas and his colleagues showed that acute and chronic elevated levels of angiotensin II resulted in an increased pool of HSPCs.
And when the researchers administered anti-angiotensin therapy, the pool of HSPCs decreased in mice and humans with SCD.
“These results indicate a new role for angiotensin in hematopoietic stem and progenitor cell trafficking under pathological conditions and define the hematopoietic consequences of anti-angiotensin therapy in vascular disease and sickle cell disease,” Dr Cancelas said.
“Every year, millions of patients receive anti-angiotensin therapies due to the harmful effects associated with chronic hyperangiotensinemia in cardiac, renal, or liver failure. Our study shows that this anti-angiotensin therapy modulates the levels of circulating stem cells and progenitors.”
In the second paper, published in Cell Reports, Dr Cancelas and his colleagues examined the role that p62 plays in HSPC mobilization.
The investigators found that, when p62 is lost in osteoblasts, mice develop a condition similar to osteoporosis in humans.
The osteoblasts cannot degrade inflammatory signals coming from macrophages. And as a consequence, the deficient osteoblasts secrete inflammatory signals that impair the retention of HSPCs in the bone marrow and allow their escape to the circulation.
Specifically, the team found that macrophages activate osteoblastic NF-kB, which results in osteopenia and HSPC egress. And p62 negatively regulates osteoblastic NF-kB activation.
Dr Cancelas noted that patients with inflammatory diseases often have osteopenia. So this research may provide insight into that phenomenon and help explain why patients with chronic inflammatory diseases have higher levels of circulating HSPCs. 
in the bone marrow
Two new studies have revealed elements that are key to hematopoietic stem and progenitor cell (HSPC) mobilization.
In one study, investigators discovered that elevated levels of the peptide hormone angiotensin II increases HSPC mobilization in the context of vasculopathy and sickle cell disease (SCD).
In the other study, researchers found that p62, an autophagy regulator and signal organizer, is required to maintain HSPC retention in the bone marrow.
Jose Cancelas, MD, PhD, of the University of Cincinnati College of Medicine in Ohio, is the corresponding author on both studies.
In the first paper, published in Nature Communications, Dr Cancelas and his colleagues noted that patients with vasculopathies have an increase in circulating HSPCs.
“This phenomenon may represent a stress response contributing to vascular damage repair,” he said. “So the question becomes, how can we learn from these patients?”
Using mouse models of vasculopathy and vasculopathy-associated SCD, Dr Cancelas and his colleagues showed that acute and chronic elevated levels of angiotensin II resulted in an increased pool of HSPCs.
And when the researchers administered anti-angiotensin therapy, the pool of HSPCs decreased in mice and humans with SCD.
“These results indicate a new role for angiotensin in hematopoietic stem and progenitor cell trafficking under pathological conditions and define the hematopoietic consequences of anti-angiotensin therapy in vascular disease and sickle cell disease,” Dr Cancelas said.
“Every year, millions of patients receive anti-angiotensin therapies due to the harmful effects associated with chronic hyperangiotensinemia in cardiac, renal, or liver failure. Our study shows that this anti-angiotensin therapy modulates the levels of circulating stem cells and progenitors.”
In the second paper, published in Cell Reports, Dr Cancelas and his colleagues examined the role that p62 plays in HSPC mobilization.
The investigators found that, when p62 is lost in osteoblasts, mice develop a condition similar to osteoporosis in humans.
The osteoblasts cannot degrade inflammatory signals coming from macrophages. And as a consequence, the deficient osteoblasts secrete inflammatory signals that impair the retention of HSPCs in the bone marrow and allow their escape to the circulation.
Specifically, the team found that macrophages activate osteoblastic NF-kB, which results in osteopenia and HSPC egress. And p62 negatively regulates osteoblastic NF-kB activation.
Dr Cancelas noted that patients with inflammatory diseases often have osteopenia. So this research may provide insight into that phenomenon and help explain why patients with chronic inflammatory diseases have higher levels of circulating HSPCs.
in the bone marrow
Two new studies have revealed elements that are key to hematopoietic stem and progenitor cell (HSPC) mobilization.
In one study, investigators discovered that elevated levels of the peptide hormone angiotensin II increases HSPC mobilization in the context of vasculopathy and sickle cell disease (SCD).
In the other study, researchers found that p62, an autophagy regulator and signal organizer, is required to maintain HSPC retention in the bone marrow.
Jose Cancelas, MD, PhD, of the University of Cincinnati College of Medicine in Ohio, is the corresponding author on both studies.
In the first paper, published in Nature Communications, Dr Cancelas and his colleagues noted that patients with vasculopathies have an increase in circulating HSPCs.
“This phenomenon may represent a stress response contributing to vascular damage repair,” he said. “So the question becomes, how can we learn from these patients?”
Using mouse models of vasculopathy and vasculopathy-associated SCD, Dr Cancelas and his colleagues showed that acute and chronic elevated levels of angiotensin II resulted in an increased pool of HSPCs.
And when the researchers administered anti-angiotensin therapy, the pool of HSPCs decreased in mice and humans with SCD.
“These results indicate a new role for angiotensin in hematopoietic stem and progenitor cell trafficking under pathological conditions and define the hematopoietic consequences of anti-angiotensin therapy in vascular disease and sickle cell disease,” Dr Cancelas said.
“Every year, millions of patients receive anti-angiotensin therapies due to the harmful effects associated with chronic hyperangiotensinemia in cardiac, renal, or liver failure. Our study shows that this anti-angiotensin therapy modulates the levels of circulating stem cells and progenitors.”
In the second paper, published in Cell Reports, Dr Cancelas and his colleagues examined the role that p62 plays in HSPC mobilization.
The investigators found that, when p62 is lost in osteoblasts, mice develop a condition similar to osteoporosis in humans.
The osteoblasts cannot degrade inflammatory signals coming from macrophages. And as a consequence, the deficient osteoblasts secrete inflammatory signals that impair the retention of HSPCs in the bone marrow and allow their escape to the circulation.
Specifically, the team found that macrophages activate osteoblastic NF-kB, which results in osteopenia and HSPC egress. And p62 negatively regulates osteoblastic NF-kB activation.
Dr Cancelas noted that patients with inflammatory diseases often have osteopenia. So this research may provide insight into that phenomenon and help explain why patients with chronic inflammatory diseases have higher levels of circulating HSPCs.