It's a pretty long pdf (12 pages). So here are some key bits:
ABSTRACT: Structural changes known as airway remodeling (AWR) characterize chronic/severe asthma and contribute to lung dysfunction. Thus, we assessed the in vivo efficacy of induced pluripotent stem cell and mesenchymoangioblast-derived mesenchymal stem cells (MCA-MSCs) on AWR in a murine model of chronic allergic airways disease (AAD)/asthma. Female Balb/c mice were subjected to a 9-wk model of ovalbumin (OVA)- induced chronic AAD and treated intravenously or intranasally with MCA-MSCs from weeks 9 to11. Changes in airway inflammation (AI), AWR, and airway hyperresponsiveness (AHR) were assessed. OVA-injured mice presented with AI, goblet cell metaplasia, epithelial thickening, increased airway TGF-b1 levels, subepithelial myofibroblast and collagen accumulation, total lung collagen concentration, and AHR (allP< 0.001 vs.uninjured control group). Apart from epithelial thickness, all other parameters measured were significantly, although not totally, decreased by intravenous delivery of MCA-MSCs to OVA-injured mice. In comparison, intranasal delivery of MCA-MSCs to OVA-injured mice significantly decreased all parameters measured (allP< 0.05 vs. OVA group) and, most notably, normalized aberrant airway TGF-b1 levels, airway/lung fibrosis, and AHR to values measured in uninjured animals. MCA-MSCs also increased collagen-degrading gelatinase levels. Hence, direct delivery of MCA-MSCs offers great therapeutic benefit for the AWR and AHR associated with chronic AAD.—Royce, S. G., Rele, S., Broughton, B. R. S., Kelly, K., Samuel, C. S. Intranasal administration of mesenchymoangioblast-derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease.
A nice summary of Cymerus in the Intro:
Cynata Therapeutics have used Cymerus technology to differentiate human induced pluripotent stem cells (iPSCs) into precursor cells known as mesenchymoangioblasts (MCAs; a class of early clonal mesoendodermal precursor cells) and subsequently into mesenchymal stem cells (MCA-MSCs) (26). Because iPSCs can proliferate indefinitely and because MCAs can expand into extremely large quantities of MSCs, sufficient MCA-MSCs can be acquired from a single Master Cell Bank of iPSCs derived from a single healthy blood donor (limiting donor- and expansion-dependent variability and contamination from nontarget cells) without the need for excessive culture expansion once MSCs are formed.
More from the Discussion:
This represents the first study to assess such effects of MCA-derived MSCs in this in vivo setting because previous studies had evaluated the in vivo therapeutic effects of these cells in a hindlimb ischemicinjurymodel (33). Both IV and IN administration ofMCA-MSCs protected against the established AI, AWR (goblet cell metaplasia, aberrant airway TGF-b1 levels, subepithelial myofibroblast and collagen accumulation, total lung collagen concentration), and AHR that was induced by repeated OVA sensitization and challenge to mice (Table 1). However, the direct delivery of MCA-MSCs into the lungs of chronically allergic mice via the IN route was seen to offer greater protection against the OVA-induced increase in airway epithelial thickness and TGF-b1 levels, subepithelial myofibroblast and collagen accumulation, total lung collagen concentration, and AHR compared with IV delivery of these cells. This resulted in the complete reversal of aberrant airway TGF-b1 levels, airway/lung fibrosis, and AHR over a 2- wk (once weekly) treatment period and a significant increase collagen-degrading MMP-9 levels by IN delivery of MCA-MSCs (Table 1). Just as importantly, neither route of MCA-MSC administration was found to affect basal expression of the parameters measured, suggesting that IN delivery of MCA-MSC offers a safe and effective means of treating the central components of asthma.
...
A striking finding that separates these MCA-MSCs from other stem cells previously studied is that otherMSCs/stem cells only produced similar effects to MCA-MSCs when applied in combination with other therapies (15, 28).
The FASEB journal article
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