Ex vivo expanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms.
BACKGROUND
Although dermal wounds are common, treatment remains limited and largely ineffective. Recent studies suggest that therapeutic application of progenitor cells is useful for tissue regeneration.


OBJECTIVE
We here investigated the effects exerted by the recently characterized immortalized haematopoietic progenitor cell line DKmix and their conditioned medium in a murine wound healing model.


RESULTS
Injection of both DKmix cells and their conditioned medium accelerated wound repair between days 3 and 10 compared with PBS-injected control mice (n = 8, P < 0.01 DKmix cells vs control, P < 0.01 conditioned medium vs control at day 6). The treated groups exhibited more CD31(+)-capillaries at day 6 after injury compared with the control group (n = 4, P < 0.01 DKmix cells vs control, P < 0.001 conditioned medium vs control), whereas there was no change in infiltrated CD68(+) macrophages. Conditioned medium of DKmix cells induced tube formation of human endothelial cells in Matrigel assays (n = 4-6, P < 0.05 conditioned medium vs control) as well as migration (n = 4, P < 0.01 conditioned medium vs control) and proliferation of murine 3T3 fibroblasts (n = 5, P < 0.05 conditioned medium vs control). Abundant levels of matrix metalloproteinase -2 and -9 in the supernatants were detected. Protein arrays of the supernatants revealed a strong secretion of cytokines and growth factors, such as monocyte chemoatractant protein-1 and GM-CSF from DKmix cells.


CONCLUSIONS
DKmix cells improve skin-substitute wound healing by promoting angiogenesis as well as migration and proliferation of fibroblasts. These data suggest that immortalized haematopoietic progenitor cells significantly improve dermal wound healing by paracrine effects.
Templin
Christian
C
Cardiovascular Center, Cardiology, University Hospital Zürich, Zürich, Switzerland. Christian.Templin@usz.ch
Grote
Karsten
K
Schledzewski
Kai
K
Ghadri
Jelena-Rima
JR
Schnabel
Sabine
S
Napp
Lars Christian
LC
Schieffer
Bernhard
B
Kurzen
Hjalmar
H
Goerdt
Sergij
S
Landmesser
Ulf
U
Koenen
Wolfgang
W
Faulhaber
Jörg
J