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Fibreus weefsel. Vasculaire gladde spier. Arterieel endothelium. MAPCellen and vasculaire ziektes. Arterieel endothelium? Vasculaire gladde spier? Bioartificiele arterie? In vivo therapie voor bvb. gangreen?. TGF- b 1 +/- PDGF-BB induces functional (v)SMCs from MAPCellen. I (pA/pF).

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Fibreus weefsel

Vasculaire gladde spier

Arterieel endothelium


Mapcellen and vasculaire ziektes
MAPCellen and vasculaire ziektes

Arterieel endothelium?

Vasculaire gladde spier?

Bioartificiele arterie?

In vivo therapie voor bvb. gangreen?


TGF-b1 +/- PDGF-BB induces functional (v)SMCs from MAPCellen

I (pA/pF)

RAOSMC

rMAPC

I (pA/pF)

Passage 1

Day 0

Day 2

Day 6

SM22

SM22a

Pass 1 TGF-b1 + PDGF-BB

SMaActin

I (pA/pF)

F-rMAPC

Day 6

Pass 1

SMaActin

RAOSMC

SM22

IgG Specific antibody

JEFF ROSS, J Clin Invest 2006


Mapcellen and vaatziektes
MAPCellen and vaatziektes

Arterieel endothelium: JA

Vasculaire gladde spier: JA

Bioartificiele arterie?

In vivo therapie voor bvb. gangreen?


Mapcel gladde spier kan contractiele tube vormen

Week 5

Rat Aorta

MAPCel-gladde spier kan “contractiele” tube vormen

Week 5, no mech. cond.

MAPC-SMCs + fibrin gel into tubular cavity

Cells are entrapped in “gel” formed around a nonadhesive mandrel

Cell-induced gel contraction around mandrel

CollagenNucleiFibrin

JEFF ROSS, JCI 2006


Conditioneren van de tube om contractiliteit te verhogen

MAPC-SMC ring constructs are subjected to cyclic distention for 3 weeks at 5% strain, 0.5 Hz, and 12.5% duty cycle

JEFF ROSS, JCI 2006


ET-1

ET-1

10 mg

5 min

30 mg

5 min

MAPC-SMC

Mechanical

MAPC-SMC

Static

MAPCel-gladde spier tube kan samentrekken en relaxeren zoals arterieel bloedvat

Traces of MAPC-SMC rings

60 mM KCl

60 mM KCl

50 mg

Rho-Kinase inhibitor relaxation

5 min

10 mM ACh

60 mM KCl 10 mM Y-27632

MAPC-SMC

Static

MAPC-SMC

Mechanical

Rho-Kinase

Inhibitor

MAPC-SMC

Mechanical

Vasodilation

JEFF ROSS, JCI 2006


  • Arterie?

  • Moet kunnen druk van ~1,000mmHg weerstaan; Momenteel ~300mmHg

  • Hoe creeren we endothelium aan binnenzijde?

  • Heel waarschijnlijk niet goed gehecht, en laat loss door “sheer” stress van bloed

  • Moeten ervoor zorgen dat er geen klonters ontstaan


Mapcellen and vasculaire ziektes1
MAPCellen and vasculaire ziektes

Arterieel endothelium: JA

Vasculaire gladde spier: JA

Bioartificiele arterie? NOG NIET

In vivo therapie voor bvb. gangreen?


Perifeer ischemie model

Acute Ischemie:

Femorale arterie geligeerd

Onmiddelijke behandeling

“Chronische” Ischemie;

~ klassieke perifere vasculaire insufficientie

Iliacale arterie geligeerd

Behandeling 5 dagen later

extensieve celdood, fibrose en verlies van lidmaat

Minimale celdood

Luttun et al J Clin Invest In Press