Macro- or microencapsulation of pig islets to cure type 1 diabetes

Table 1 Bioartificial device configurations for encapsulation of pig islets

	Macroencapsulation	Microencapsulation	Conformal coating
Type of pig islets tested	Adult/neonate	Adult/neonate	Adult
Suitable material with biocompatibility	Alginate	Alginate with/ without PLL/PLO over-layer	PEG
Implantation site	Intraperitoneal	Intraperitoneal	Into the liver via the portal vein
	Subcutaneous	Kidney subcapsular space
Proof of concept in preclinical studies in diabetic primates	+	+	−
Maximum survival of pig islets and diabetes correction	Mean 24 wk correction of glycated hemoglobin < 7% after transplantation of the MCD into subcutaneous tissues	Max 804 d but never reproduced; Biocompatibility confirmed under the kidney capsule up to 6 mo after transplantation	ND
Clinical study	+	+	ND
Clinical efficacy	No insulin-independence Glycated hemoglobin improvement; porcine insulin detected in recipient sera up to 4 yr after transplantation with insulin positive cells into hollow-fiber devices.	No insulin independence Survival up to 9.5 yr with insulin-positive cells after transplantation into the peritoneum and detection of urinary porcine C-peptide up to 11 mo after transplantation	ND
Advantages for large-scale clinical application	Easy procedure for transplantation into subcutaneous tissue	Easy procedure for transplantation by simple injection into the peritoneum	- Capability of transplantation into the liver
	Simple procedure to remove the graft from subcutaneous tissue	Large scale encapsulation of large number of islets	- Reduction of graft size
Limitations for large-scale clinical application	Limited islet oxygenation	Large volume of encapsulated islets limiting transplantation into the peritoneum	- No stability for long-term islet immunoprotection
	Difficulty to transplant into the peritoneal cavity	Islet survival limited by absence of biologic interaction with encapsulation material
		No ability to remove the graft after transplantation

PLL: Poly-lysine; PLO: Poly-ornithine; MCD: Monolayer cellular device; ND: Not determined; PEG: Polyethylene glycol.