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A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation.

Ballios BG, Cooke MJ, Donaldson L, Coles BL, Morshead CM, van der Kooy D, Shoichet MS - Stem Cell Reports (2015)

Bottom Line: The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA.Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function.The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

No MeSH data available.


Related in: MedlinePlus

Mice Transplanted with Cells Suspended in HAMC Recover from Stroke Injury(A) Experimental paradigm shows that mice are tested for the foot fault assay 3 days prior to stroke to establish a baseline and 3 days after stroke to detect the behavioral deficit. At 4 days after stroke, cells are transplanted into the lesion site, and mice are tested 14 and 28 days later (i.e., at 18 and 32 days after stroke, respectively).(B) At 3 days after injury, foot fault increases significantly in all animal groups except uninjured controls (n = 8). At 18 and 32 days after injury, foot fault significantly decreases to pre-injury, baseline values for mice that had NSCs delivered in HAMC (p < 0.05, n = 7). In contrast, mice that had NSCs delivered in aCSF (n = 7) and control mice that had aCSF or HAMC injected without cells (n = 12) did not show a significant recovery relative to the functional deficit (i.e., at 3 days). Only mice transplanted with NSCs in HAMC showed behavioral recovery at 14 and 28 days relative to the functional deficit at 3 days.(C) Representative images of immunohistochemical stained brain tissue, at 28 days after transplantation, show that most of the transplanted NSCs delivered in HAMC are GFAP+ astrocytes, with few NeuN+ neurons and few Olig2+ oligodendrocytes. The majority of transplanted NSCs in HAMC have differentiated into GFAP-expressing astrocytes.(D) NSCs delivered in HAMC have significantly greater tissue penetration than do those delivered in aCSF at both 0 and 28 days after transplantation (n = 4, p < 0.05, p < 0.01, respectively).For all graphs, mean ± SEM are plotted, n independent transplants.
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fig7: Mice Transplanted with Cells Suspended in HAMC Recover from Stroke Injury(A) Experimental paradigm shows that mice are tested for the foot fault assay 3 days prior to stroke to establish a baseline and 3 days after stroke to detect the behavioral deficit. At 4 days after stroke, cells are transplanted into the lesion site, and mice are tested 14 and 28 days later (i.e., at 18 and 32 days after stroke, respectively).(B) At 3 days after injury, foot fault increases significantly in all animal groups except uninjured controls (n = 8). At 18 and 32 days after injury, foot fault significantly decreases to pre-injury, baseline values for mice that had NSCs delivered in HAMC (p < 0.05, n = 7). In contrast, mice that had NSCs delivered in aCSF (n = 7) and control mice that had aCSF or HAMC injected without cells (n = 12) did not show a significant recovery relative to the functional deficit (i.e., at 3 days). Only mice transplanted with NSCs in HAMC showed behavioral recovery at 14 and 28 days relative to the functional deficit at 3 days.(C) Representative images of immunohistochemical stained brain tissue, at 28 days after transplantation, show that most of the transplanted NSCs delivered in HAMC are GFAP+ astrocytes, with few NeuN+ neurons and few Olig2+ oligodendrocytes. The majority of transplanted NSCs in HAMC have differentiated into GFAP-expressing astrocytes.(D) NSCs delivered in HAMC have significantly greater tissue penetration than do those delivered in aCSF at both 0 and 28 days after transplantation (n = 4, p < 0.05, p < 0.01, respectively).For all graphs, mean ± SEM are plotted, n independent transplants.

Mentions: To test functional efficacy, behavioral recovery of Et-1 stroke-injured mice was evaluated for NSCs delivered into the stroke lesion site in either HAMC or aCSF versus vehicle-alone and uninjured controls. Animals were evaluated by foot-fault assay 3 days prior to stroke to establish a baseline and 3 days after Et-1-induced stroke to examine the functional deficit. In mice that displayed a functional deficit, NSCs were transplanted 1 day later (i.e., 4 days after stroke), and behavior was evaluated biweekly for 4 weeks (Figure 7A). Mice treated with either aCSF or HAMC alone or NSCs suspended in aCSF showed some, but not significant, recovery relative to the functional deficit observed with stroke injury (at 3 days post-stroke). In contrast, mice transplanted with NSCs delivered in HAMC showed significant recovery at both 2 and 4 weeks (p < 0.05; Figure 7B). Uninjured mice showed no significant difference between time points. Following study completion, the number of animals with surviving cells was evaluated. When NSCs were transplanted in HAMC, 70% (7 of 10) of the animals had surviving cells, whereas only 58% (7 of 12) of the animals transplanted with NSCs in aCSF had surviving cells (Figure S6D). Notwithstanding the functional benefit observed, cells transplanted in HAMC were mostly glial fibrillary acidic protein (GFAP)-positive cells at 4 weeks. Few NeuN+ neurons (Sui et al., 2012) and few Olig2+ oligodendrocytes (Menn et al., 2006) were observed (Figure 7C). Notably, the maximal depth of tissue penetration of NSCs delivered in HAMC was significantly greater than that of NSCs delivered in aCSF both immediately and 4 weeks after transplantation (p ≤ 0.05; Figure 7D).


A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation.

Ballios BG, Cooke MJ, Donaldson L, Coles BL, Morshead CM, van der Kooy D, Shoichet MS - Stem Cell Reports (2015)

Mice Transplanted with Cells Suspended in HAMC Recover from Stroke Injury(A) Experimental paradigm shows that mice are tested for the foot fault assay 3 days prior to stroke to establish a baseline and 3 days after stroke to detect the behavioral deficit. At 4 days after stroke, cells are transplanted into the lesion site, and mice are tested 14 and 28 days later (i.e., at 18 and 32 days after stroke, respectively).(B) At 3 days after injury, foot fault increases significantly in all animal groups except uninjured controls (n = 8). At 18 and 32 days after injury, foot fault significantly decreases to pre-injury, baseline values for mice that had NSCs delivered in HAMC (p < 0.05, n = 7). In contrast, mice that had NSCs delivered in aCSF (n = 7) and control mice that had aCSF or HAMC injected without cells (n = 12) did not show a significant recovery relative to the functional deficit (i.e., at 3 days). Only mice transplanted with NSCs in HAMC showed behavioral recovery at 14 and 28 days relative to the functional deficit at 3 days.(C) Representative images of immunohistochemical stained brain tissue, at 28 days after transplantation, show that most of the transplanted NSCs delivered in HAMC are GFAP+ astrocytes, with few NeuN+ neurons and few Olig2+ oligodendrocytes. The majority of transplanted NSCs in HAMC have differentiated into GFAP-expressing astrocytes.(D) NSCs delivered in HAMC have significantly greater tissue penetration than do those delivered in aCSF at both 0 and 28 days after transplantation (n = 4, p < 0.05, p < 0.01, respectively).For all graphs, mean ± SEM are plotted, n independent transplants.
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fig7: Mice Transplanted with Cells Suspended in HAMC Recover from Stroke Injury(A) Experimental paradigm shows that mice are tested for the foot fault assay 3 days prior to stroke to establish a baseline and 3 days after stroke to detect the behavioral deficit. At 4 days after stroke, cells are transplanted into the lesion site, and mice are tested 14 and 28 days later (i.e., at 18 and 32 days after stroke, respectively).(B) At 3 days after injury, foot fault increases significantly in all animal groups except uninjured controls (n = 8). At 18 and 32 days after injury, foot fault significantly decreases to pre-injury, baseline values for mice that had NSCs delivered in HAMC (p < 0.05, n = 7). In contrast, mice that had NSCs delivered in aCSF (n = 7) and control mice that had aCSF or HAMC injected without cells (n = 12) did not show a significant recovery relative to the functional deficit (i.e., at 3 days). Only mice transplanted with NSCs in HAMC showed behavioral recovery at 14 and 28 days relative to the functional deficit at 3 days.(C) Representative images of immunohistochemical stained brain tissue, at 28 days after transplantation, show that most of the transplanted NSCs delivered in HAMC are GFAP+ astrocytes, with few NeuN+ neurons and few Olig2+ oligodendrocytes. The majority of transplanted NSCs in HAMC have differentiated into GFAP-expressing astrocytes.(D) NSCs delivered in HAMC have significantly greater tissue penetration than do those delivered in aCSF at both 0 and 28 days after transplantation (n = 4, p < 0.05, p < 0.01, respectively).For all graphs, mean ± SEM are plotted, n independent transplants.
Mentions: To test functional efficacy, behavioral recovery of Et-1 stroke-injured mice was evaluated for NSCs delivered into the stroke lesion site in either HAMC or aCSF versus vehicle-alone and uninjured controls. Animals were evaluated by foot-fault assay 3 days prior to stroke to establish a baseline and 3 days after Et-1-induced stroke to examine the functional deficit. In mice that displayed a functional deficit, NSCs were transplanted 1 day later (i.e., 4 days after stroke), and behavior was evaluated biweekly for 4 weeks (Figure 7A). Mice treated with either aCSF or HAMC alone or NSCs suspended in aCSF showed some, but not significant, recovery relative to the functional deficit observed with stroke injury (at 3 days post-stroke). In contrast, mice transplanted with NSCs delivered in HAMC showed significant recovery at both 2 and 4 weeks (p < 0.05; Figure 7B). Uninjured mice showed no significant difference between time points. Following study completion, the number of animals with surviving cells was evaluated. When NSCs were transplanted in HAMC, 70% (7 of 10) of the animals had surviving cells, whereas only 58% (7 of 12) of the animals transplanted with NSCs in aCSF had surviving cells (Figure S6D). Notwithstanding the functional benefit observed, cells transplanted in HAMC were mostly glial fibrillary acidic protein (GFAP)-positive cells at 4 weeks. Few NeuN+ neurons (Sui et al., 2012) and few Olig2+ oligodendrocytes (Menn et al., 2006) were observed (Figure 7C). Notably, the maximal depth of tissue penetration of NSCs delivered in HAMC was significantly greater than that of NSCs delivered in aCSF both immediately and 4 weeks after transplantation (p ≤ 0.05; Figure 7D).

Bottom Line: The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA.Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function.The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

No MeSH data available.


Related in: MedlinePlus