Myogenic Precursors from iPS Cells for Skeletal Muscle Cell Replacement Therapy

Abstract

The use of adult myogenic stem cells as a cell therapy for skeletal muscle regeneration has been attempted for decades, with only moderate success. Myogenic progenitors (MP) made from induced pluripotent stem cells (iPSCs) are promising candidates for stem cell therapy to regenerate skeletal muscle since they allow allogenic transplantation, can be produced in large quantities, and, as compared to adult myoblasts, present more embryonic-like features and more proliferative capacity in vitro, which indicates a potential for more self-renewal and regenerative capacity in vivo. Different approaches have been described to make myogenic progenitors either by gene overexpression or by directed differentiation through culture conditions, and several myopathies have already been modeled using iPSC-MP. However, even though results in animal models have shown improvement from previous work with isolated adult myoblasts, major challenges regarding host response have to be addressed and clinically relevant transplantation protocols are lacking. Despite these challenges we are closer than we think to bringing iPSC-MP towards clinical use for treating human muscle disease and sporting injuries.

Differentiation and sarcomere formation in skeletal myocytes directly prepared from human induced pluripotent stem cells using a sphere-based culture

“…Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have received much attention because of their potential use for cell-based therapies and in vitro modeling (Hosoyama et al, 2012; Rinaldi and Perlingeiro, 2014; Roca et al, 2015). Human iPSCs, established from somatic cells, represent a valuable source of tissue for generating human myogenic progenitors (Tedesco and Cossu, 2012).…”

“…Human iPSCs, established from somatic cells, represent a valuable source of tissue for generating human myogenic progenitors (Tedesco and Cossu, 2012). Furthermore, these progenitors are able to form myotubes in culture, which can provide a useful platform for understanding normal muscle development and disease mechanisms in vitro (Hosoyama et al, 2012; Rinaldi and Perlingeiro, 2014; Roca et al, 2015). …”

Activation of the NLRP3 Inflammasome Is Associated with Valosin-Containing Protein Myopathy

“…Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells (as reviewed in [19, 20]. Human iPSCs express stem cell markers and are capable of generating cells characteristic of all three germ layers (i.e.…”

“…Generation of skeletal muscle cells from iPSCs as an in vitro model and for therapy of muscular dystrophies has recently been reported [20]. Three VCP-associated iPSC cell lines harboring the R155H mutation and three control cell lines were used [19, 20]. …”

Micropatterned substrates with physiological stiffness promote cell maturation and Pompe disease phenotype in human induced pluripotent stem cell‐derived skeletal myocytes

“…The advent of human pluripotent stem cells (PSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provides an indefinite cell source for cell‐based therapies and in vitro modeling (Hosoyama, Van Dyke, & Suzuki, ; Rinaldi & Perlingeiro, ; Roca, Requena, Edel, & Alvarez‐Palomo, ). Specifically, human skeletal myogenic progenitors can be derived from human PSCs (Tedesco & Cossu, ; Zhu et al, ) using either exogenous expression of myogenic genes such as PAX3 , PAX7 , and MYOD (Abujarour et al, ; Darabi et al, ; Maffioletti et al, ; Skoglund et al, ; Tanaka et al, ) or small molecules and growth factors (Barberi et al, ; Borchin, Chen, & Barberi, ; Caron et al, ; Chal et al, ; I. Y. Choi et al, ; Hosoyama, McGivern, Van Dyke, Ebert, & Suzuki, ; Hwang et al, ; Shelton et al, ; Xu et al, ).…”