Table 1.

Stretch-induced changes in fibroblast proliferation, apoptosis and morphology

Response	Main findings	Cell type	Coating and plate	Stretch machine	Stretch pattern	Stretch duration	Serum	Reference
Increased proliferation	Small proliferation increase with stretch	NRVF	Collagen-coated silicone membrane	Homemade stretch device	20% uniaxial	24 h	Serum-free	Sadoshima et al., (1992)132
	Proliferation increased by stretch	NRVF	Collagen-coated silicone membrane plate	Flexcell∗	1-Hz, 30%	24 h and 48 h	Serum-free	Cao and Gardner, (1995)91
	Increased fibroblast proliferation with low stretch (2%) for 24 or 72 h. In high-stretch conditions (8%), increased only at 24 h	Human atrial fibroblast	Fibronectin	Homemade stretch device	1-Hz, 2% or 8% uniaxial	24 h and 72 h	NS	Ugolini et al., (2016)92
	Increase in proliferation of stretched fibroblasts seeded on low stiffness substrate (3 kPa), and in fibroblasts cultured with medium from stretched cardiomyocytes	Adult mouse ventricular fibroblast	Collagen I-coated polyacrylamide gel on PDMS membrane	Homemade stretch device	Static, 3% or 6% uniaxial	24 h and 48 h	10%-FBS	Herum et al., (2017)90
	Increased proliferation with low stretch+hypoxia (1%-O2), no stretch+hypoxia and low stretch+physoxia (6%-O2)	Human ventricular fibroblast	Fibronectin	Homemade stretch device	1-Hz, 2% or 8% uniaxial	24 h	NS	Ugolini et al., (2017)87
No change or decreased proliferation	Decreased proliferation after 12-h stretch in 10% FBS-containing medium. No change with longer stretch or 1% FBS	Foetal RCF	Elastin-coated plate	Flexercell∗ FX-2000	1.5-Hz, 20% equibiaxial	8–88 h	0%, 1%, or 10% FBS	Butt and Bishop, (1997)89
	Decreased proliferation after stretch. Fibroblasts stopped at G2/M; increased p21, decreased cyclin-B1	Neonatal RCF	Collagen-coated silicone membrane	Modified from Lee et al., 1996131	20% sustained stretch	1, 4, 12, 24 h	10% FBS	Liao et al., (2004)88
	Decreased proliferation by 12-h stretch regardless of ECM substrate. Decrease most marked on randomly organized collagen	Neonatal RCF	Fibronectin-, laminin-, collagen-coated and uncoated charged silicone elastic membrane	Modified from Yost et al., 2000101	0.08 Hz, 5% uniaxial	12 h	10% NBS + 5% FBS	Atance et al., (2004)86
	Decreased proliferation with high strain (8% stretch) for 72 h	Human atrial fibroblast	Fibronectin	Homemade stretch device	1 Hz, 2% or 8% uniaxial	24 h and 72 h	NS	Ugolini et al., (2016)92
	Decreased proliferation on high substrate stiffness (8 kPa)	Adult mouse ventricular fibroblast	Collagen I-coated polyacrylamide gel, polydimethylsiloxane membrane	Homemade stretch device	Static, 3% or 6% uniaxial	24 h and 48 h	10% FBS	Herum et al., (2017)90
	No change with no-stretch+physoxia (6%-O2) or high-strain stretch (8%)+physoxia	Human ventricular fibroblast	Fibronectin	Homemade device	1 Hz, 2% or 8% uniaxial	24 h	NS	Ugolini et al., (2017)87
Apoptosis	No cell death or apoptosis	NRVF	Collagen I	Flexercell FX-2000	1 Hz, 20% equiaxial	24, 48, 96 h	2.5% FBS	Persoon-Rothert et al., (2002)98
	No apoptosis	Neonatal RCF	Rat tail collagen-coated silicone membrane	Modified from Lee et al., 1996131	20% sustained stretch	1, 4, 12, 24 h	10% FBS	Liao et al., (2004)88
	Few apoptotic genes differentially expressed in stretched fibroblasts; >15% apoptotic genes increased in myocyte-enriched fractions	NRVF	Collagen I	Flexercell FX-2000	1 Hz, 20% equiaxial	24 h	2.5% FBS	Boerma et al., (2005)99
Morphology	Cells elongated, oriented, perpendicular to the direction of stretch	Neonatal RCF	Laminin-coated silicone elastomer membranes	Homemade stretch device	10 cycles/min, 10% uniaxial stretch	72 h	NS	Terracio et al., (1988)78
	Cells rotated to align more perpendicular to the direction of stretch	Neonatal RCF	Aligned collagen-coated silicone membrane	Homemade stretch device	3%, 6%, 12% uniaxial; 0, 5, 10 cycles/min	12 h	5% FBS + 10% NBS	Yost et al., (2000)101
	Cells surface area increased on all ECM substrates	Neonatal RCF	Fibronectin-, laminin-, collagen-coated; uncoated charged silicone elastic membrane	Modified from Yost et al., 2000101	0.08 Hz, 5% uniaxial	1, 5, and 10 min	10% NBS + 5% FBS	Atance et al., (2004)86
	Cell margin ruffling, disorganization of long actin stress fibres, retraction of cortical cytoplasm. Effects that are immediate, persisted over time	Neonatal RCF	Laminin-coated silastic membrane	Modified from MacKenna et al., 200076	5% equibiaxial	0, 1.25, 2.5, 5, 10, 20, and 40 min	10% FBS + 5% NBS	Fuseler et al., (2007)100

ECM, extracellular matrix; FBS, foetal bovine serum; NBS, newborn bovine serum; NRVF, neonatal rat ventricular fibroblasts; NS, not stated; RCF, rat cardiac fibroblasts.

^*Please note that this company has used both Flexcell and Flexercell as names; we have retained the usage in each paper cited.