Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema

Abstract

We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.

Mesenchymal Stromal Cells to Regenerate Emphysema: On the Horizon?

“…In the study of Antunes et al [30], injection of L-MSCs via the right jugular vein led to the death of all injected mice, which was not observed after intravenous administration of either A-MSCs or BM-MSCs in this study. In contrast, intravenous injection of L-MSCs into the tail vein, as demonstrated by Hoffman et al [25], did not lead to lethality.…”

“…Only BM-MSCs displayed beneficial systemic effects, while A-MSCs and L-MSCs showed a more significant reduction in the fractional area of alveolar collapse than BM-MSCs [30]. Another study compared human L-MSCs and BM-MSCs in vitro and observed that L-MSCs expressed higher levels of the stemness-related marker nestin, which may have consequences for their ability to differentiate into different cell types [31].…”

“…With respect to the delivery route, in contrast to intravenous administration, intratracheal MSC administration further reduced alveolar hyperinflation and the collagen fiber content in this model [30]. Engraftment, survival, and persistence of administered MSCs were in vestigated in 11 of the 16 animal studies included in this review [18, 21, 23-25, 28, 32-36], using methods such as fluorescence tracking or using cross-gender administration of MSCs.…”

CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

“…As previously described, animals received either HLFs ( n = 6), mMSCs ( n = 6), BMDMCs ( n = 13), or BMDMCs depleted of either CD45 ( n = 6), CD34 ( n = 6), CD3 ( n = 6), CD19 ( n = 6), CD11b ( n = 9), CD31 ( n = 6), or Sca-1 ( n = 6) cells (Fig. 1B) [16, 19, 20, 24, 25, 35, 36]. …”

Best of Milan 2017—repair of the emphysematous lung: mesenchymal stromal cell and matrix

“…from different sources were compared, even when cells have similar proliferation and differentiation capacities (9). As an example, BM derived-MSCs are able to inhibit the release of pro-inflammatory cytokines and stimulate the functional activity of regulatory T-lymphocytes (10,11).…”