Immunological Barriers to Stem Cell Therapy in the Central Nervous System

Table 1

(a)

Source	Year	Transplants			Recipients
		Species	Strain	Tissue used	Species	Strain	Location
Nicholas et al. [40]	1987	Mice	BALB/cANC	Embryonic neocortex; These cells do not express MHC I.	Mice	BALB/cANC; 6–8-week-old female mice	Right lateral ventricle
			CBA/J
			E15–18
		Results
		Significantly more inflammatory cells in allogeneic than in syngeneic grafts. There were some T cells in the allogeneic grafts, but not syngeneic grafts. More neurons survive in syngeneic versus allogeneic grafts. There is less necrosis as well.
Lawrence et al. [41]	1990	Rat	PVG	Embryonic hippocamus	rat	AO	Hippocampus
			AO	(E18–20)-no MHC I
		Results
		Allografts were rejected by both macrophages and cytotoxic T cells. Grafts were infiltrated early (3–6 d) by host microglia especially in necrotic tissue surrounding the graft. Blood vessels begin to join the graft to the host as early as 1 day. Lymphocytes, macrophages, and microglia begin to accumulate around the larger vessels. MHC I expression is turned on 3–6 days after transplanting. Most cells in the allografts were rejected by cytotoxic T cells by 27 d.

(b)

Source	Year	Transplants		Recipients			Number of cells
		Species	Cell type	Species	Strain	Location
Rémy et al. [50]	2001	Pig	Aortic endothelial cells from 30 d old pigs express both MHC I and MHC II	Rat	LEW.1A	Striatum	400,000
		Pig	Embryonic neurons from ventral mesencephalon e25–28 express little or no MHC I.				400,000
		Results
		Endothelial cells were rejected quickly (3–7 days) by primarily macrophage/microglia cells. Neurons were rejected much later (14–21 days) by both macrophages and cytotoxic lymphocytes.

(c)

Source	Year	Transplants			Recipients			Number of cells
		Species	Strain	Cell type	Species	Strain	Location
Coyne et al. [42]	2006	Rat	Sprague-	Bone marrow MSCs; from eGFP rats.	Rat	Sprague-Dawley	Striatum or; hippocampus	50,000
			Dawley
		Sprague-Dawley rats are outbred instead of inbred so these are allogeneic grafts and not syngeneic (225 g females).
		Results
		Few GFP-positive MSCs were seen at either location at 7 days and almost none at 14 days after transplanting. MSCs elicited an inflammatory response. Activated macrophages and microglia were seen in the grafts.
Tambuyzer et al. [43]	2009	Mice	C57BL/6	Marrow stromal cells	Mice	FVB	Intracerebral; right pelvic limb muscle	200,000
		Results
		Stromal cells are lost over 3-4 weeks. Activation of microglia cells (CD11b). Muscle grafts were rejected by T cells, but not cerebral grafts.
Chen et al. [44]	2011	Mice	C57BL/6	Neural progenitor cells that express eGFP from CAG promoter	Mice	C57BL/6	Hippocampus	100,000
						Balb/c
		Results
		Fewer GFP-positive cells in allogeneic grafts as compared to syngeneic. More activated microglia in allografts than syngeneic one. Neurogenesis is inhibited in allografts. This effect is reversed with NSAIDs.
Spears [47]	2011	Mice	129svj	Neuralized ESCs	Mice	129svj	Left striatum	1,000,000
				expressing eGFP.		CD-1
		Results
		Allografts were rejected quickly (5–7 days) by cytotoxic T cells. Little activated microglia were detected. Syngeneic grafts increase in size.