MR‐guided pulsed focused ultrasound improves mesenchymal stromal cell homing to the myocardium

Abstract

Image‐guided pulsed focused ultrasound (pFUS) is a non‐invasive technique that can increase tropism of intravenously (IV)‐infused mesenchymal stromal cells (MSC) to sonicated tissues. MSC have shown promise for cardiac regenerative medicine strategies but can be hampered by inefficient homing to the myocardium. This study sonicated the left ventricles (LV) in rats with magnetic resonance imaging (MRI)‐guided pFUS and examined both proteomic responses and subsequent MSC tropism to treated myocardium. T2‐weighted MRI was used for pFUS targeting of the entire LV. pFUS increased numerous pro‐ and anti‐inflammatory cytokines, chemokines, and trophic factors and cell adhesion molecules in the myocardial microenvironment for up to 48 hours post‐sonication. Cardiac troponin I and N‐terminal pro‐B‐type natriuretic peptide were elevated in the serum and myocardium. Immunohistochemistry revealed transient hypoxia and immune cell infiltration in pFUS‐targeted regions. Myocardial tropism of IV‐infused human MSC following pFUS increased twofold‐threefold compared with controls. Proteomic and histological changes in myocardium following pFUS suggested a reversible inflammatory and hypoxic response leading to increased tropism of MSC. MR‐guided pFUS could represent a non‐invasive modality to improve MSC therapies for cardiac regenerative medicine approaches.

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

“…This included improved survival in a model of cisplatin induced acute kidney injury (AKI) (90), and improvement in reperfusion and a reduction in fibrosis in a model of critical limb ischemia (Figure 4) (91). Most recently, this procedure was shown to also be successful for enhancing homing to the myocardium in the left ventricle in a rat model, indicating the potential of this approach for cardiac regeneration (92). It has been proposed that FUS induces Ca influx via mechanosensitive calcium channels (TRPC1), leading to activation of the NFkβ pathway and transient expression of TNFα.…”

Barriers to immune cell infiltration in tumors

“…T-FUS can stimulate release of inflammatory cytokines including IL-12, IFNγ, and TNFα. [130][131][132][133] In normal tissues, M-FUS has upregulated ICAM-1 and VCAM-1, improving mesenchymal stem cell homing to muscle [134][135][136] and also upregulated E-selectin, P-selectin, and ICAM-1. 137 138 In murine melanoma and breast cancer models, M-FUS has transiently upregulated expression of ICAM-1, VCAM-1, and multiple pro-inflammatory cytokines, but not in a manner sufficient to yield robust T cell infiltration into these tumors.…”

Ways to increase the regenerative potential of mesenchymal stromal cells

“…Аналогичное действие оказывает и имитация гипоксии введением хлорида кобальта (в сочетании с ингибированием CXCR4) [74]. Сообщалось также о возможности мобилизации МСК в кровоток с помощью электроакупунктурного воздействия, предположительно за счет активации гипоталамуса и симпатической нервной системы [83] и привлечения их в поврежденную область путем обработки последней ультразвуком, усиливающим локальную продукцию хемоаттрактантов [84]. Стимуляцией миграции МСК через кровоток в поврежденные ткани могут быть обусловлены и прорегенеративные свойства ряда биологически активных веществ растительного происхождения, таких как каннабиноиды, протокатехиновая кислота, проантоцианидины, флавоноиды [85].…”