B. Cell-Matrix Interactions A How cells pull onto and deform the matrix to which they attach themselves B Cell-matrix interactions control the spontaneous closure of wounds in organs C. What happens when regeneration is induced?
B. Cell-Matrix Interactions A. How cells pull onto and deform the matrix to which they attach themselves. B. Cell-matrix interactions control the spontaneous closure of wounds in organs. C. What happens when regeneration is induced?
B. Cell-matrix interactions control the spontaneous closure of wounds in organs. 1. Hypothesis: Regeneration requires selective blocking of contraction. Need for understanding of kinetics and mechanism of contraction(to be tested later) 2. Initiation of contractile force, Defect perimeter or center of skin defect? 3. Propagation of contraction Do cells cooperate? 4. Termination of contraction How does the contractile force die out?
B. Cell-matrix interactions control the spontaneous closure of wounds in organs. 1. Hypothesis: Regeneration requires selective blocking of contraction. Need for understanding of kinetics and mechanism of contraction (to be tested later). 2. Initiation of contractile force. Defect perimeter or center of skin defect? 3. Propagation of contraction. Do cells cooperate? 4. Termination of contraction. How does the contractile force die out?
2 Initiation of contractile force Located at defect perimeter or uniformly distributed? Picture frame vs, uniform contractile field UCF)hypotheses Data in Fig. 9.2(attached) show that the ECM analog that blocks contraction is effective at perimeter but not at center of defect These data support the picture frame hy pothesis However, other data(Fig. 4.4) support the UCF hypothesis
2. Initiation of contractile force. Located at defect perimeter or uniformly distributed? • Picture frame vs. uniform contractile field (UCF) hypotheses. • Data in Fig. 9.2 (attached) show that the ECM analog that blocks contraction is effective at perimeter but not at center of defect. • These data support the picture frame hypothesis. • However, other data (Fig. 4.4) support the UCF hypothesis
Spontaneously contracting dermis-free defect (10 d) Contractile cells stained brown Two magnifications Image removed due to copyright considerations
Spontaneously contracting dermis-free defect (10 d). Contractile cells stained brown. Two magnifications. Image removed due to copyright considerations. Image removed due to copyright considerations
Contraction of dermis- free defect blocked by drt Image removed due to copyright considerations Brown, contractile cells. Blue-gray, porous DRT
Contraction of dermis-free defect blocked by DRT Brown, contractile cells. Blue-gray, porous DRT. Image removed due to copyright considerations
DRT is a Effect of biologic- DRT ally location on active contraction ECM blocking analog Image removed due to copyright considerations See Figure 9.2 in Yannas, L.V. Tissue and Organ Regeneration in Adults New York Springer-Verlag, 2001
DRT is a biologically active ECM analog Effect of DRT location on contraction blocking Image removed due to copyright considerations. See Figure 9.2 in Yannas, I. V. Tissue and Organ Regeneration in Adults. New York: Springer-Verlag, 2001. Image removed due to copyright considerations. See Figure 9.2 in Yannas, I. V. Tissue and Organ Regeneration in Adults. New York: Springer-Verlag, 2001
3. Propagation of contraction Do cells cooperate? Cell cluster at edge of defect reaches thickness of about 100 um at time of contraction initiation (Fig. 9.3, attached) Contraction is more vigorous when cell density inside pores is high(Fig. 10.4, attached)
3. Propagation of contraction. Do cells cooperate? • Cell cluster at edge of defect reaches thickness of about 100 µm at time of contraction initiation (Fig. 9.3, attached). • Contraction is more vigorous when cell density inside pores is high (Fig. 10.4, attached)
Cells(F) 2 d post-injury form cluster, thickness 8 located at Image removed due to copyright considerations edge of See Figure 9. 3 in [Yannas] skin defect δ Increases 6 d post-injury after injury
Cells (F) form cluster, thickness δ, located at edge of skin defect. δ increases after injury. 2 d post-injury Image removed due to copyright considerations. See Figure 9.3 in [Yannas]. Image removed due to copyright considerations. See Figure 9.3 in [Yannas]. 6 d post-injury
Compare two ECM analogs with different activity Image removed due to copyright considerations See Table 10.1 in [Yannas]
Compare two ECM analogs with different activity. Image removed due to copyright considerations. See T able 10.1 in [Yannas]. Image removed due to copyright considerations. See T able 10.1 in [Yannas]
Cell density high inside pores of ECM Image removed due to copyright considerations analog See Figure 10.4-top image in [Yannas (analog B) that blocks contraction poorly
Cell density high inside pores of ECM analog (analog B) that blocks contraction poorly Image removed due to copyright considerations. See Figure 10.4 – top image in [Yannas]. Image removed due to copyright considerations. See Figure 10.4 – top image in [Yannas]
