Table 1.

Stem cell transplantation experiments in man and animal models grouped by donor cell phenotype

Reference	Host	Injury	Donor cell phenotype	Route of administration	Time after injury	Number of cells	Outcome	Follow‐up
Yang et al. 2002	Friend leukaemia virus strain B mice	LAD ligation	mES (ES‐D3)‐derived early differentiated cardiomyo‐ cytes, transfected with GFP and ± transfected with VEGF	Epicardial into BZ and infarct 3 × 10 µl	15 min	3 × 105	Significant increase in function & capillary density. Stem cells transfected with VEGF > increase than stem cells alone > than controls	6 weeks
Behfar et al. 2002	Sprague‐Dawley/Wistar	LAD ligation	mES (CGR8)‐derived cardiomyocytes	Epicardial into BZ 27G needle	4 weeks	3 × 105	Significant increase in LVEF on echocardiography	5 weeks
Min et al. 2000b	Wistar rats	LAD ligation	mES (ES‐D3)‐derived cardiomyocytes, transfected with GFP	Epicardial into BZ and infarct 3 × 10 µl	30 min	3 × 104	Significant functional improvement, compared with controls. Engrafted GFP +ve cardiomyocytes seen	6 weeks
Klug et al. 1996	Mdx adult mice	None	mES (ES‐D3 transfected MHC‐neor/pGK‐transgene) derived cardiomyocytes	Epicardial 30G tuberculin syringe	N/A	1 × 104	Cardiomyocytes engrafted, no measures of function	N/A
Perin et al. 2003	Humans	Congestive cardiac failure/IHD	Autologous BM, Mononuclear cells separated, avg 2.4%CD45lowCD34+	Percutaneous transendocardial catheter	N/A	25.5 ± 6.3 ×106 cells	NYHA, CCS improved, EF significantly improved 20–29%, SPECT less stress defects	2 & 4 months
Tse et al. 2003	Humans	IHD	Autologous BM, Mononuclear cells separated 3.2%CD34+ 27G needle, 16 injections @11 sites	NOGA mapping, Endomyocardial injection via catheter	N/A	1.4 × 107	Less angina attacks, reduced GTN tablet requirement, MRI: improved target wall thickening & motion	3 months
Pak et al. 2003	Pigs	LAD distal occlussion	MSC & BM or BM only	Direct epicardial, injection, × 15	1 month	1.5 × 108 MSC, BM N/A	Higher nerve density in MSC group	60 & 96 days
Nishida et al. 2003	Dark agouti syngenic rats	LAD ligation	Aspirated BM	Direct epicardial injection, 6 × 10 µl, 26G needle	Stat	6 × 107	Increase in FS, microvessel density & blood flow & 90 days	7, 30, 60
Strauer et al. 2002	Humans	Acute myocardial infarction	Autologus mononuclear cells from BM aspiration, Ficoll gradient, 2.1%CD34+, 0.6% AAC133+	IC catheter, 6–7 injections 2–3 mls per injection, each 1.5–4 × 106 cells	5–9 days	18 × 106 cells	Repeat cardiac catheter significant reduction in hypo/dys/akinetic segments, improved perfusion on thallium, no significant increase in EF	3 months
Hamano et al. 2002	Dogs	LAD ligation, permanent	Autologus BM, density centrifugation	Direct epicardial, 6 injections, 0.1 ml each 27G needle	30 days	12 × 107	Improved wall thickening & density of microvessels in marginal area	30 days some up to 240
Hamano et al. 2001	Humans	IHD	Autologus mononulcear cells separated from BM aspiration	Endocardial at CABG, avg 11 injections 0.1 mL each, 26G needle	N/A	5 × 108−1 × 109 cells	60% improved stress tests	1 year
Kobayashi et al. 2000	Inbred dark agouti rats	LAD ligation	Unsorted BM	Direct epicardial injection, 6 × 10 µl PBS	1 h	5 × 106	Siginificant increase in No. of vessels	1, 3 & 7 days
Tomita et al. 1999	Sprague‐Dawley rats	LV cryoinjury	BM separated with Percoll gradient, fresh, cultured 7 days or 5‐azacytidine treated	Direct epicardial injection, 50 µl into centre of scar, tuberculin syringe	3 weeks	106	All grps significant increase capillaries, significant increase peak systolic & developed pressure only in BM treated with azacytidine	5 weeks
Orlic et al. 2001a	C57BL/6 mice	LAD ligation	Aspirated BM, sorted for Lin−c‐kit+, from male transgenic eGFP mice	Direct epicardial injection, 2.5 µl into border zones	3–5 h	1.5 × 104–1 × 105	Improved LV haemodynamics, 68% of infarct engrafted with transplanted cells	9 days
Orlic et al. 2001b	C57BL/6 mice	LAD ligation	None	G‐CSF & SCF 5 days prior & 3 days post injury	N/A	N/A	Increase in survival, EF, & regenerating myocardium seen	27 days
Jackson et al. 2001	Irradiated mice	LAD ligation 60 mins	SP cells separated from Rosa C57BL/16 mice, CD34−/low, c‐kit+ Sca‐1+	BM transplant	10 weeks prior	2000 for transplant	Engrafted cells of which, 0.02% cardiomyocytes, 3.3% endothelial cells	2 & 4 weeks
Mangi et al. 2003	Sprague‐Dawley rats	LAD ligation	MSCs CD117+, CD90+, CD34−, transfected with GFP, LacZ or Akt	Direct epicardil injection, × 5 injections into border zone	60 min	2.5 or 5 × 106	MSC with Akt group complete normalization of function, 80–90% regeneration of myocardium	2 weeks
Thompson et al. 2003	Pigs	None	Aspirated BM, adherent cells, transfected with GFP	Transendocardial, 15 injections	N/A	N/A	GFP + ve cells found in all animals, no adverse outcome	0–28 days
Gojo et al. 2003	C3H/HeJ adult mice	None	BM stromal cells, treated with 5‐Azacytidine, CD34low/– c‐kit+,CD140a+	Direct epicardial injection, 31G needle, 10 µl in ventricle or IVC	N/A	106	0.25% of cells engrafted	1, 4, 8 & 12 weeks
Shake et al. 2002	Pigs	LAD ligation, 60 mins	Aspirated BM, MSC separated	Direct epicardial, 6 injections, 0.5 ml each 30G needle	2 weeks	6 × 107 cells	Significant increase systolic function, Transdifferentiation	2 & 4 weeks
Min et al. 2002a	Pigs	LAD ligation	Human MSCs & human Fetal cardiomyocytes	Endocardial injection, BZ	5 min	7 × 106 cells	Transdifferentiation, improved haemodynamics & improved blood flow (microspheres)	6 weeks
Toma et al. 2002	CB17 SCID/ Beige mice	None	hMSC, transfected with LacZ	Transdiaphragm epicardial injection, 100 µls 32G needle	N/A	0.5–1 × 106	Up to 0.44% engraftment, transdifferentiation	30 mins, 4, 14, 21, 30 & 60 days
Stamm et al. 2003	Humans	Myocardial infarction	Autologous, BM aspiration, AC133+ cells separated by MACS	Endocardial at CABG, × 10 injections 0.2 mls, 22G needle	10 days 3 months	1 × 106	No long‐term adverse effects, Improved NYHA, Improved LVEF (minimal). Improved perfusion on SPECT	avg 6.5 months
Assmus et al. 2002	Humans	Acute myocardial infarction	BM mononuclear cells, 90% endothelial characteristics VEGFR2, CD105, PECAM‐ 1, vWF, VE‐Cadherin & CD146	Intracoronary, ballon inflated for 3 ×, 3, 3 mls per patient	4 days	245 × 106, 7 × 106CD34+/CD45+	EF improved significant, Reduced WMA, improved CFR, improved viability FDG‐PET	4 months
Kocher et al. 2001	Athymic nude rats Sprague‐ Dawley	LAD ligation permnt	BM aspiration CD34+ve separated, Dil labelled	Tail vein injection	48 h	2 × 106 cells	Significant improvement EF	2 & 15 week
Kawamoto et al. 2001	Athymic nude rats, Hsd: RH‐rnv	LAD ligation, Permnt	Peripheral blood MNCs, Dil labelled	Tail vein injection	3 h	106	Significant increase in FS & capillary density, improved regional wall motion, transdifferentiation	28 days
Kamihata et al. 2001	ePigs	LAD ligation	Aspirated BM, MNC separated, transfected with GFP	Epicardial injection, BZ & infarct, 25 × 0.02 mls	1 h	108 cells	Significant increase EF, blood flow, vessels on angio & histology, decreased perfusion defects	3 weeks & 12 week
Fuchs et al. 2001	Pigs	LCx ameroid implant	Aspirated BM, MNC separated	Transendocardial injection, 10–12 injections 0.2 mls each	4 week	N/A	Improved regional contractility, perfusion & EF	1, 3, 7 & 21 days

BM, bone marrow; BZ, border zone (of infarct); CABG, coronary artery bypass graft; CCS, Canadian cardiovascular score (for angina); EF, ejection fraction; FS, fractional shortening; GFP, green fluorescent protein; IC, intra‐coronary; IHD, ischaemic heart disease; LAD, left anterior descending artery; LV, left ventricle; Mdx, muscular dystrophy; mES, murine embryonic stem cell; MNC, mononuclear cell; MRI, magnetic resonance imaging; NYHA, New York Heart Association (score for heart failure); PBS, phosphate‐buffered saline; PET, positron emission tomography; SPECT, single photon emission computed tomography; VEGF, vascular endothelial growth factor.