Transplantation of Skeletal Muscle-Derived Sca-1(+)/PW1(+)/Pax7(-) Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction

We have previously shown that skeletal muscle-derived Sca-1+/PW1+/Pax7− interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 105 eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (p < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (p < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (p < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (p < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapies

Transplantation of Skeletal Muscle-Derived Sca-1⁺/PW1⁺/Pax7⁻ Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction

We have previously shown that skeletal muscle-derived Sca-1⁺/PW1⁺/Pax7⁻ interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 10⁵ eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (\u1d631 < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (\u1d631 < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (\u1d631 < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (\u1d631 < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapie

Can a Soft Robotic Probe Use Stiffness Control Like a Human Finger to Improve Efficacy of Haptic Perception?

When humans are asked to palpate a soft tissue to locate a hard nodule, they regulate the stiffness, speed, and force of the finger during examination. If we understand the relationship between these behavioral variables and haptic information gain (transfer entropy) during manual probing, we can improve the efficacy of soft robotic probes for soft tissue palpation, such as in tumor localization in minimally invasive surgery. Here, we recorded the muscle co-contraction activity of the finger using EMG sensors to address the question as to whether joint stiffness control during manual palpation plays an important role in the haptic information gain. To address this question, we used a soft robotic probe with a controllable stiffness joint and a force sensor mounted at the base to represent the function of the tendon in a biological finger. Then, we trained a Markov chain using muscle co-contraction patterns of human subjects, and used it to control the stiffness of the soft robotic probe in the same soft tissue palpation task. The soft robotic experiments showed that haptic information gain about the depth of the hard nodule can be maximized by varying the internal stiffness of the soft probe

The role of morphological computation of the goat hoof in slip reduction

The remarkable ability of goats to maintain stability during climbing cliffs or trees provides a valuable opportunity to understand some of the secrets of stable legged locomotion on unstructured terrains. This paper, for the first time, presents analytical and experimental explanations as to how the morphological computation at the goat hoof makes a significant contribution to slip reduction on both smooth and rough surfaces. We conducted experiments using a laboratory made hoof and compared its dynamic behavior against a rounded foot. We recorded forces and position of the hoof to analyze the effect of its shape and the individual contributions from 3-joints in the hoof on the work required to slip. Results state that the work required to move the hoof is more than 3 times that required to move a rounded foot. Additionally, the variables in the transient state are affected not only by the number and type of joints but also by the interaction with the environment. These findings promote the development of new types of feet for robots for all terrain conditions with greater stability and less control complexity

Morphological computation of haptic perception of a controllable stiffness probe

When people are asked to palpate a novel soft object to discern its physical properties such as texture, elasticity, and even non-homogeneity, they not only regulate probing behaviors, but also the co-contraction level of antagonistic muscles to control the mechanical impedance of fingers. It is suspected that such behavior tries to enhance haptic perception by regulating the function of mechanoreceptors at different depths of the fingertips and proprioceptive sensors such as tendon and spindle sensors located in muscles. In this paper, we designed and fabricated a novel two-degree of freedom variable stiffness indentation probe to investigate whether the regulation of internal stiffness, indentation, and probe sweeping velocity (PSV) variables affect the accuracy of the depth estimation of stiff inclusions in an artificial silicon phantom using information gain metrics. Our experimental results provide new insights into not only the biological phenomena of haptic perception but also new opportunities to design and control soft robotic probes

A biologically inspired multimodal whisker follicle

Mammalian whisker follicle contains multiple sensory receptors strategically organized to capture tactile sensory stimuli of different frequencies via the vibrissal system. There have been a number of attempts to develop robotic whiskers to perform texture classification tasks in the recent past. Inspired by the features of biological whisker follicle, in this paper we design and use a novel soft whisker follicle comprising of two different frequency-dependent data capturing modules to derive deeper insights into the biological basis of tactile perception in the mammalian whisker follicle. In our design, the innervations at the Outer Conical Body (OCB) of a biological follicle are realized by a piezoelectric transducer for capturing high frequency components; whereas the innervations around the hair Papilla are represented by a hall sensor to capture low frequency components during the interaction with the environment. In this paper, we show how low dimensional information such as the principle components of co-variation of these two sensory modalities vary for different speeds and indentations of brushing the whisker against a surface. These new insights into the biological basis of tactile perception using whiskers provides new design guidelines to develop efficient robotic whiskers