Hematopoietic Contribution to Skeletal Muscle Regeneration in Acid α-Glucosidase Knockout Mice

Abstract

Recent studies have shown that cells from bone marrow (BM) can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved remain unknown. We performed BM transplantation in acid alpha-glucosidase (GAA) knockout mice, a model of glycogen storage disease type II, and our observations suggested that the BM cells contribute to skeletal muscle fiber formation. Furthermore, we showed that most CD45+:Sca1+ cells have a donor character in regenerating muscle of recipient mice. Based on these findings, CD45+:Sca1+ cells were sorted from regenerating muscles. The cell number was increased with granulocyte colony-stimulating factor after cardiotoxin injury, and the cells were transplanted directly into the tibialis anterior (TA) muscles of GAA knockout mice. Sections of the TA muscles stained with anti-laminin-alpha2 antibody showed that the number of CD45+:Sca1+ cells contributing to muscle fiber formation and glycogen levels were decreased in transplanted muscles. Our results indicated that hematopoietic stem cells, such as CD45+:Sca1+ cells, are involved in skeletal muscle regeneration.

Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases

“…Gaa (−/−) (Raben et al, 1998) + + AAV (Rucker et al, 2004;Zhu et al, 2005;Gatto et al, 2017;Puzzo et al, 2017), BMT (Mori et al, 2008), Chaperone (Khanna et al, 2012(Khanna et al, , 2014, ERT (Raben et al, 2001(Raben et al, , 2002(Raben et al, , 2010Xu et al, 2004), SRT (Ashe et al, 2010;Douillard-Guilloux et al, 2010) Gaa ( Cln2 (−/−) (Sleat et al, 2004) + + AAV (Sondhi et al, 2008;Chen et al, 2009), Anti-Apoptosis (Kim et al, 2009), ERT (Kim et al, 2008;Sleat et al, 2008;Meng et al, 2012) CLN3 Ceroid lipofuscinosis, neuronal 3…”

“…Two authentic murine Gaa(-/-) models have been established, and both of them have analogous pathology to the human disease with hallmarks such as muscle weakening and gait abnormalities (Bijvoet et al, 1998;Raben et al, 1998). The models have proven useful in pre-clinical trials with a variety of treatments including gene therapy, BMT, PCT, ERT and glycogen accumulation suppression (Raben et al, 2001(Raben et al, , 2002(Raben et al, , 2010Rucker et al, 2004;Xu et al, 2004;Zhu et al, 2005;Mori et al, 2008;Khanna et al, 2014;Gatto et al, 2017;Puzzo et al, 2017).…”

Author's Response to “Donor-derived Hematopoietic Cell Contribution to Myofibers in Acid α-Glucosidase Deficiency: A Promising Progress or Back to the Beginning?”

“…We would like to respond to the letter by Dr. Yablonka-Reuveni. This letter questioned the method we used to assay acid α-glucosidase (GAA) and therefore the interpretation of our results (Mori et al 2008). We probed our Western blots with rabbit IgG to human urine GAA, a protein with a molecular mass of 64 kDa (Raben et al 1998).…”

Donor-derived Hematopoietic Cell Contribution to Myofibers in Acid α-Glucosidase Deficiency

“…The recent issue of the Journal of Histochemistry & Cytochemistry (JHC) reports a new study about hematopoietic contribution to skeletal muscle regeneration in acid a-glucosidase (GAA) knockout mice (Mori et al 2008). The GAA knockout mouse serves as a model of glycogen storage disease type II (GSDII, also known as Pompe disease).…”

“…The new publication in the JHC by Mori and colleagues (2008) again brings this controversial topic to the fore. The authors transplanted bone marrow cells from eGFP mice into GAA knockout mice and interpreted their findings as evidence that the engrafted bone marrow cells contributed to skeletal muscle fiber formation.…”