Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26989084
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26989084
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Mol+Pharmacol
2016 ; 89
(6
): 630-44
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell
Transplantation
#MMPMID26989084
Kazemi Z
; Bergmayr C
; Prchal-Murphy M
; Javaheri T
; Themanns M
; Pham HT
; Strohmaier W
; Sexl V
; Freissmuth M
; Zebedin-Brandl E
Mol Pharmacol
2016[Jun]; 89
(6
): 630-44
PMID26989084
show ga
Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and
progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a
prostacyclin analog approved for the treatment of pulmonary hypertension, can be
repurposed to improve hematopoietic stem cell transplantation. Murine and human
HSPCs were isolated from bone marrow and umbilical cord blood, respectively.
Prostanoid receptor agonists and the combination thereof with forskolin were
tested for their capacity to stimulate [(3)H]cAMP accumulation in HSPCs. Three
independent approaches were employed to verify the ability of agonist-activated
HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The
underlying mechanism was explored in cellular migration assays and by blocking
C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists
tested in combination with forskolin, treprostinil was most efficacious in
raising intracellular cAMP levels in murine and human HPSCs. Injection of murine
and human HSPCs, which had been pretreated with treprostinil and forskolin,
enhanced survival of lethally irradiated recipient mice. Survival was further
improved if recipient mice were subcutaneously administered treprostinil (0.15 mg
kg(-1) 8 h(-1)) for 10 days. This regimen also reduced the number of HSPCs
required to rescue lethally irradiated mice. Enhanced survival of recipient mice
was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs.
Treprostinil stimulates the engraftment of human and murine hematopoietic stem
cells without impairing their capacity for self-renewal. The investigated dose
range corresponds to the dose approved for human use. Hence, these findings may
be readily translated into a clinical application.
free
free
free
