Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 2004 Mar;164(3):773–779. doi: 10.1016/S0002-9440(10)63165-3

Adult Bone Marrow-Derived Stem Cells in Muscle Connective Tissue and Satellite Cell Niches

Patrick A Dreyfus *, Fabrice Chretien *, Bénédicte Chazaud *, Youlia Kirova †, Philippe Caramelle *, Luis Garcia ‡, Gillian Butler-Browne §, Romain K Gherardi *
PMCID: PMC1613267  PMID: 14982831

Abstract

Skeletal muscle includes satellite cells, which reside beneath the muscle fiber basal lamina and mainly represent committed myogenic precursor cells, and multipotent stem cells of unknown origin that are present in muscle connective tissue, express the stem cell markers Sca-1 and CD34, and can differentiate into different cell types. We tracked bone marrow (BM)-derived stem cells in both muscle connective tissue and satellite cell niches of irradiated mice transplanted with green fluorescent protein (GFP)-expressing BM cells. An increasing number of GFP+ mononucleated cells, located both inside and outside of the muscle fiber basal lamina, were observed 1, 3, and 6 months after transplantation. Sublaminal cells expressed unambiguous satellite cell markers (M-cadherin, Pax7, NCAM) and fused into scattered GFP+ muscle fibers. In muscle connective tissue there were GFP+ cells located close to blood vessels that expressed the ScaI or CD34 stem-cell antigens. The rate of settlement of extra- and intralaminal compartments by BM-derived cells was compatible with the view that extralaminal cells constitute a reservoir of satellite cells. We conclude that both muscle satellite cells and stem cell marker-expressing cells located in muscle connective tissue can derive from BM in adulthood.

In the late 1990s, adult bone marrow (BM) cells were shown to contain stem cells that can give rise to skeletal muscle fibers in vivo.1,2 BM cell derivation of muscle fibers was assessed by the expression of either a lacZ transgene under the control of a muscle-specific promoter in normal mice1 or dystrophin in mdx mice.2 Therefore, induction of terminal myogenic differentiation was necessary to detect BM-derived cells, and, consistently, cells situated upstream from the myofiber in the muscle cell lineage could not be visualized. Now, this difficulty can be overcome by tracking BM-derived stem cells after BM transplantation with labeled cells from transgenic donor mice that constitutively express the green fluorescent protein (GFP).3

Evidence of a muscle stem-cell hierarchy came from the study of Pax7−/− mice.4 The muscles of these mice contain a normal number of multipotent stem cells but lack so-called satellite cells. This points to at least two distinct compartments in the muscle stem cell hierarchy: 1) the compartment of satellite cells that are resident cells found in an anatomical niche located beneath the muscle fiber basal lamina; these extensively studied cells mainly express specific markers of committed muscle precursor cells, such as M-cadherin and Pax7, and ensure postnatal skeletal muscle growth and regeneration through a well-documented sequence of activation, proliferation, and fusion events;5 and 2) the recently described compartment of interstitial muscle stem cells,6 that are extralaminal,6,7 express the stem cell markers CD346,7 and ScaI6,8,9 but not the markers of committed myogenic cells, and can differentiate into various cell constituents of the muscle tissue, eg, myogenic cells, endothelial cells, and adipocytes.6,7,10 Several authors have suggested that interstitial muscle stem cells may constitute a reservoir of satellite cells.6,8 Whether these cells reside and self-renew in muscle connective tissue from embryonic stages or can be recruited from BM during postnatal life remains undetermined.6,8

In the present study, we tracked BM-derived stem cells in both muscle connective tissue and satellite cell niches in irradiated mice transplanted with GFP-expressing BM-cells. We used immunocytochemistry on muscle tissue sections for position markers (basal lamina antigens), a panel of myogenic cell markers, the stem cell antigens CD34 and ScaI, and other cell-specific markers.

Materials and Methods

Mouse Strain

B6 (C57BL/6) mice were transplanted with BM-derived cells from B6TgGFP transgenic mice [C57BL/6 TgN(actEGFP)Osb YO1] in which the GFP transgene is expressed under the control of a nontissue-specific promoter, chicken β-actin with cytomegalovirus enhancer, as a cytoplasmic protein.11 In B6TgGFP mice, both BM cells and muscle fibers constitutively express GFP. Therefore, after BM transplantation, GFP may serve as an unambiguous marker for donor-derived cells in host muscle. B6 and B6TgGFP mice were housed in our level 2 biosafety animal facility and received food and water ad libitum. Before manipulations, animals were anesthetized using an intraperitoneal injection of chloral hydrate. This study was conducted in accordance with the European Community guidelines for animal care (Journal Officiel des Communutés Européennes, L358, December 18, 1986).

BM Transplantation

Briefly, donor BM cells were obtained by flushing femurs of B6TgGFP mice with Dulbecco’s modified Eagle’s medium (Invitrogen, Paisley, UK), and washed twice in cold phosphate-buffered saline (PBS, Invitrogen). Retro-orbital injection of 3 to 5 × 107 BM cells in 0.1 ml of mouse serum and PBS (1:1), was done in 9.0-Gy-irradiated, 4-week-old B6 mice (60Co γ-rays within 1 day before BM transplantation). After transplantation, mice received 10 mg/kg/day ciprofloxacin for 4 weeks to prevent infection during the aplastic phase.

Flow Cytometry Analysis

To quantify the amount of engraftment, the peripheral blood mononuclear cells of transplanted mice were analyzed by flow cytometry using a XL cytometer (Beckman-Coulter, Hialeah, FL) before sacrifice, ie, at 1, 3, and 6 months after transplantation. Leukocytes were gated on, and GFP fluorescence was measured under the fluorescein isothiocyanate channel. All analyses and quantitation were performed using the System II software from Beckman-Coulter.

Tissue Preparation

Paraformaldehyde fixation was used to retain GFP within cells, rapid loss of the GFP signal being observed in fresh-frozen sections. At sacrifice time mice were anesthetized and sequentially transcardially perfused with PBS and buffered 4% paraformaldehyde. Whole muscle groups were then gently removed, postfixed in 4% paraformaldehyde for 2 hours, and soaked in 10% sucrose in PBS for 2 hours and then in 30% sucrose overnight at 4°C. Whole muscle samples were snap-frozen in embedding medium (Tissue-Tek; Sakura) and serial 7-μm-thick cryosections were performed. All sections were then coverslipped with Vectashield mounting medium for fluorescence (Vector Laboratories, Burlingame, CA) with or without a nuclear counterstaining by 4,6-diamidino-2-phenylindole. Images were captured on a Zeiss Axiophot microscope (Carl Zeiss Inc., Germany) with an Orca ER digital camera (Hamamatsu Photonics, Japan) using Simple PCI (C-Imaging, Compix Inc.) software.

Immunohistochemistry

In all these experiments, muscle sections were gently trypsinized for 10 minutes at 37°C using commercial trypsin-ethylenediaminetetraacetic acid (Invitrogen) for antigen retrieval. Samples were blocked for 20 minutes in PBS/20% fetal calf serum/0.3% Triton X-100 (Sigma-Aldrich, St. Louis, MO). Primary antibodies were incubated with the sections at 37°C for 1 hour. Three 15-minute washings in PBS were performed between each incubation. Mouse monoclonal antibodies were used at the following concentrations: anti-NCAM (1:100; BD Pharmingen, San Diego, CA), anti-M-cadherin (1:100; NanoTools, Teningen, Germany), anti-Pax7 (1:100; Developmental Studies Hybridoma Bank), anti-laminin-1 (1:100, Sigma-Aldrich), anti-laminin-2 (1:100; Novocastra, New Castle Upon Tyne, UK) with M.O.M. kit (Vector Laboratories) allowing the use of mouse monoclonal antibodies for mouse tissues. The secondary antibody used was tetramethyl-rhodamine-isothiocyanate-conjugated goat anti-mouse (1:200, Jackson Laboratory, Bar Harbor, ME). We also used biotinylated rat anti-mouse antibodies to CD34 (1:50), ScaI (1:50), CD11b (1:100), and CD45 (1:50) (BD Pharmingen) revealed by tetramethyl-rhodamine-isothiocyanate-conjugated streptavidin (1:400, Vector Laboratories).

Statistical Analysis

Unpaired Student’s t-test was used for all statistical analyses (GraphPad-InStat software).

Results

Nine B6 mice transplanted with GFP+ BM cells were included in the study. All had a proportion of GFP+ peripheral blood mononucleated cells >95% as compared to donor values.

Abundant GFP+ mononuclear cells appeared in muscle tissue after transplantation (Figure 1; A to D). Their number increased from 15.9 per 100 muscle fibers at 1 month to 26.4 at 6 months (P < 0.03) in cross sections of the tibialis anterior muscle (Table 1). Labeling with anti-laminin 1 or 2 antibodies showed GFP+ mononucleated cells both inside and outside of the muscle fiber basal lamina (Figure 1B).

Figure 1.

Figure 1

Open in a new tab

Detection of GFP+ BM donor-derived cells in skeletal muscle of transplant recipient mice. Representative cross and longitudinal 7-μm sections of a fixed tibialis anterior muscle from a GFP+ BM recipient mouse analyzed by fluorescent microscopy 3 months after transplantation. A: GFP+ (green) spindle-shaped perivascular cells that do not express CD45 are shown. B: Merge image of GFP+ cells and laminin 1 (red) showing BM-derived cells in both interstitial connective tissue and sublaminal satellite cell niche (arrow). L1 refers to laminin 1. The areas where myofibers take place are labeled by asterisks. C and D: Longitudinal and cross sections of GFP+ muscle fibers. Peripheral myonuclei are seen in D. The longitudinal section shows two adjacent GFP+ muscle fibers, one with a homogenous sarcoplasmic expression of GFP and one with a heterogeneous expression suggesting distinct nuclear cytoplasmic domains because of the recent fusion of donor-derived cells with the recipient muscle fiber (C). Nuclei are labeled with 4,6-diamidino-2-phenylindole (blue). Scale bar, 10 μm.

Table 1.

Quantitation of GFP+ Monuclear Cells and Myofibers in Bone Marrow Transplant Recipient Mice

(A) Mononuclear cells quantified in cross-sections of tibialis anterior muscle
Time after transplant Animals (n) Myofibers evaluated (n) GFP+ cells (for 100 myofibers) GFP+ CD11b+/GFP+ cells (%) GFP+ satellite cells/GFP+ cells (%) GFP+ M-cad+/M-cad+ cells (%) GFP+ CD34+/CD34+ cells (%) GFP+ Sca1+/ Sca1+ cells (%) GFP+ vWF+/vWF+ cells (%)
1 month 3 970–5100 15.9 ± 1.6 37.0 ± 9.4 4.1 ± 1.0 0.9 ± 0.1 0.8 ± 0.3 0.0 ± 0.0 0.1 ± 0.2
3 months 3 800–4165 17.0 ± 3.5 35.3 ± 5.8 9.4 ± 0.9 1.7 ± 0.2 1.7 ± 0.2 0.8 ± 0.1 0.2 ± 0.1
6 months 3 830–1255 26.4 ± 5.0 33.4 ± 2.8 14.4 ± 2.3 2.6 ± 0.8 4.1 ± 0.4 1.3 ± 0.3 0.2 ± 0.1
(B) Myofibers quantified in cross-sections of various muscles
Time after transplant Animals (n) Myofibers evaluated Tibialis anterior muscle (%) Rectus abdominalis muscle (%) Soleus muscle (%) Gastrocnemius muscle (%) Diaphragm
1 month 3 5100 0.0 ± 0.0 — — — —
3 months 3 4165 0.5 ± 0.4 — — — —
6 months 3 752–1255 1.3 ± 0.8 2.6 ± 0.2 1.6 ± 0.6 1.9 ± 0.9 1.5 ± 1.0
Open in a new tab

The proportion of GFP+ cells found in a sublaminal satellite cell niche increased with time (Table 1), 4.1% of GFP+ cells being sublaminal at 1 month, 9.4% at 3 months, and 14.4% at 6 months (all P < 0.003). These cells consistently expressed M-cadherin (Figure 2; A to D), a specific satellite cell marker,5 GFP+ M-cadherin+ cells accounting for 0.9%, 1.7%, and 2.6% of M-cadherin+ cells at 1, 3, and 6 months, respectively (1 versus 6 months; P < 0.02). Moreover, some GFP+ cells distinctly expressed Pax7, a nuclear factor essential for the specification of muscle stem cells into sublaminal satellite cells4 (Figure 2; E to H), and NCAM (leu19) a marker typically expressed by satellite cells and myoblasts (Figure 2; I to L). In addition to an increasing number of GFP+ muscle satellite cells, scattered GFP+ muscle fibers appeared at 3 and 6 months after transplantation (Figure 1, C and D). At 6 months, 1.3% of fibers in the tibialis anterior muscle were GFP+. A similar percentage was observed in the four other evaluated muscle groups (Table 1). Serial cross-sections and longitudinal sections showed that GFP was either homogeneously expressed along the whole muscle fiber length (up to 1500 μm) or, occasionally, as distinct nuclear cytoplasmic domains (Figure 1C). Unlike muscle fibers undergoing regeneration after necrosis, most GFP+ muscle fibers had peripheral nuclei. These findings were consistent with fusion of GFP+ satellite cells to pre-existing fibers.

Figure 2.

Figure 2

Open in a new tab

Detection of GFP+ satellite cells exhibiting co-localization of definitive markers. Representative cross sections of fixed tibialis anterior muscles 6 months after transplantation showing co-expression of GFP and a panel of satellite cell antigens, including M-cadherin (A–D), the nuclear transcription factor Pax7 (E–H), and NCAM (I–L). Nuclei are labeled with 4,6-diamidino-2-phenylindole (blue). Each image in D, H, and L corresponds to an increasing of background to make myofibers more apparent. Scale bar, 10 μm.

In addition to the well-defined GFP+ satellite cells and muscle fibers, GFP+ mononucleated cells were found in muscle interstitial tissue. Approximately one third of GFP+ cells expressed the monocyte/macrophage lineage marker CD11b at all time points after transplantation (Table 1). In addition, GFP+ mononucleated cells expressing ScaI or CD34 were detected in the interstitial connective tissue (Figure 3; A to F), at perivascular and endomysial sites known to host multipotent muscle stem cells.6,8

Figure 3.

Figure 3

Open in a new tab

Characterization of interstitial stem cells originating from donor BM. Representative sections of fixed tibialis anterior muscles 6 months after transplantation showing co-expression of GFP and the stem cell antigens ScaI and CD34, and hematopoietic lineage marker CD45. A to C: A donor-derived ScaI+ cell is located in interstitial connective tissue close to a muscle fiber. Nuclei are labeled with 4,6-diamidino-2-phenylindole (blue). D to F: Two donor-derived CD34+cells are located in muscle connective tissue in a perivascular area. The vessel is a medium-sized artery as assessed by the presence of an autofluorescent elastic lamina observed in all wavelengths. D to F: GFP+ cells are located outside the vascular basal lamina stained with an anti-laminin 1 antibody (L1, blue). G to I: The rarely detected GFP+ cells expressing CD45 were rounded like mononuclear blood cells. Scale bar, 10 μm.

The GFP+ ScaI+ cells significantly increased in number with time (P < 0.05) but remained less numerous than GFP+ M-cadherin+ cells at all time points (Table 1, Figure 4). GFP+ ScaI+ cells were usually detected in the vicinity of large and small vessels, as previously described,8 and were not found within satellite cell niches (Figure 3; A to C). GFP+ CD34+ cells were detected throughout muscle connective tissue (Figure 3; D to F). Although CD34 was normally expressed by small vessel endothelial cells, no GFP+ CD34+ cell lining a distinct lumen or enclosed by a laminin 1-positive vascular basal lamina was detected. Consistently, a very small number of GFP+ cells expressed the von Willebrand factor endothelial cell marker (0.1 to 0.2% at the different time points). Although sublaminal CD34+ cells were occasionally seen, GFP+ CD34+ cells without basal lamina material interposed between the plasmalemma and the underlying muscle fiber were rarely detected after double staining with anti-laminin antibodies (1 of 2664 GFP+ cells). GFP+ CD34+ cells were more abundant than GFP+ ScaI+ cells and less abundant than GFP+ M-cadherin+ cells, at all time points (Figure 4).

Figure 4.

Figure 4

Open in a new tab

Respective numbers of GFP+ cells exhibiting co-localization of different markers per whole tibialis anterior muscle cross-section at various time points after transplantation. Three animals were analyzed at each time point. Results are expressed as mean ± SEM. M-Cadherin (M-Cad) was used as a satellite cell marker, ScaI and CD34 as stem cell markers, and von Willebrand factor (vWF) as an endothelial cell marker.

Interstitial GFP+ cells expressing CD45+, the exclusive marker of the hematopoietic lineage, were rarely detected and appeared rounded like mononuclear leukocytes (Figure 3; G to I). Although spindle-shaped interstitial GFP+ cells could express CD34 (Figure 3; G to I), they did not express CD45 (Figure 1A).

Discussion

In this study we observed an increasing number of BM-derived GFP+ mononucleated cells in skeletal muscle at 1, 3, and 6 months after transplantation, including satellite cells, characterized by both sublaminal location and expression of the unambiguous markers of committed myogenic cells, and interstitial cells expressing the stem cell antigens Sca-1 and CD34. These BM-derived cells were able to fuse as assessed by the formation of an increasing number of GFP+ muscle fibers.

While this study was in progress, two articles have reported the possible BM-derivation of the muscle satellite cells using GFP+ BM transplantation procedures.12,13 GFP+ satellite cells could not be identified by specific markers,12 or only expressed certain satellite cell markers such as c-met, α7-integrin, and Myf-5.13 We report herein that BM-derived satellite cells express the well-known markers M-Cad, Pax7, and NCAM.5 Moreover, previous studies used teased muscle fiber preparations, a procedure implying removal of connective tissue, thus precluding analysis of muscle interstitial cells. We extend previous observations on teased fiber preparations by demonstrating that stem cell marker-expressing cells found in connective tissue can derive from BM in adulthood.

ScaI, an early marker of murine hematopoietic stem cells14, has been previously found expressed by mononuclear cells in skeletal muscle tissue.8 Such ScaI+ cells likely constitute one phenotype of muscle multipotent stem cells,8 called side population (SP) cells based on their ability to efflux the fluorescent dye Hoechst 33342.2,15 As in the present study, they are usually observed in the vicinity of endomysial vessels8 but virtually never in subliminal location.16 Muscle Sca1+ cells have been subdivided into CD45+ hematopoietic cells and CD45− cells that contain the bulk of the myogenic activity.17 Skeletal muscle ScaI+ cells also include both CD34− and CD34+ subpopulations.18

Distribution of CD34+cells in muscle is more controversial than that of Sca1+ cells.6 Indeed, CD34 expression by satellite cells was repeatedly reported,8,19,20 but could not be substantiated by immunoelectron microscopy.6 Because CD34 is a versatile marker expressed on in vivo and in vitro activation,21,22 it is possible that the in vivo fixation we used, as did Tamaki and colleagues,6 accounted for the relatively low number of CD34+ satellite cells observed in our study as compared to teased fiber studies.8,19

As in previous studies, BM transplantation was performed in mice irradiated at 9 to 10 Gy,12,13 a dose inducing a 66% decrease of the muscle satellite cell number.13 It is, therefore, likely that muscle irradiation behaves as a conditioning procedure, emptying satellite cell niches presumably favoring their subsequent occupancy by BM-derived cells. Our experiments were conducted in standard, nonexercise-enriched, conditions. Such conditions are associated with a rather low rate of GFP+ muscle fiber formation, whereas chronic exercise can induce a marked increase of GFP+ muscle fiber density.13 In this setting, the higher settlement rate of GFP+ M-cadherin+ (satellite) cells as compared to GFP+ ScaI+ (interstitial) cells likely reflected an imbalance between cell translocation from the interstitial compartment and the slow output toward muscle fiber formation. Therefore, the remarkable accumulation of BM-derived cells into satellite cell niches indirectly supports the view that extralaminal cells constitute a reservoir of satellite cells.6

GFP+ muscle fiber formation likely resulted from fusion of BM-derived cells with existing fibers, according to a phenomenon known as myonuclear accretion.23 Unlike other tissues, such as the central nervous system, where stem cells can misleadingly fuse with differentiated cells to form tetraploid cells of unknown significance,24 BM-derived stem cells likely achieved true myogenic differentiation in skeletal muscle, as suggested by the diploid status of GFP+ satellite cells.13 The BM cell subset that may give rise to muscle fibers, ie, hematopoietic stem cells or mesenchymal stem cells or both, remains controversial.25

It is too early to decide if BM transplantation will prove useful in the treatment of patients with muscular dystrophy in the future.26 Dystrophin restoration in mdx mice after allogenic BM transplantation2,12 remains far below the levels needed to provide clinical benefits in Duchenne muscular dystrophy. It could be expected, however, that further studies aimed at characterizing the pathways for the homing of stem cells would aid in the improvement of the muscle settlement by BM cells.27,28 In addition to the fascinating new insights it provides on renewal of the skeletal muscle tissue, transplantation of GFP+ BM-derived cells constitutes an appropriate procedure to conduct such studies.

Footnotes

Address reprint requests to Patrick A. Dreyfus, EMI0011, Faculté de Médecine, 8 rue du Général Sarrail, 94000 Créteil, France. E-mail: patrick.dreyfus@creteil.inserm.fr.

Supported by the Association Française contre les Myopathies (grant no. 9319).

P.A.D. and F.C. contributed equally to this study.

References

  1. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998;279:1528–1530. doi: 10.1126/science.279.5356.1528. [DOI] [PubMed] [Google Scholar]
  2. Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999;401:390–394. doi: 10.1038/43919. [DOI] [PubMed] [Google Scholar]
  3. Manfra DJ, Chen SC, Yang TY, Sullivan L, Wiekowski MT, Abbondanzo S, Vassileva G, Zalamea P, Cook DN, Lira SA. Leukocytes expressing green fluorescent protein as novel reagents for adoptive cell transfer and bone marrow transplantation studies. Am J Pathol. 2001;158:41–47. doi: 10.1016/S0002-9440(10)63942-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;102:777–786. doi: 10.1016/s0092-8674(00)00066-0. [DOI] [PubMed] [Google Scholar]
  5. Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol. 2001;91:534–551. doi: 10.1152/jappl.2001.91.2.534. [DOI] [PubMed] [Google Scholar]
  6. Tamaki T, Akatsuka A, Ando K, Nakamura Y, Matsuzawa H, Hotta T, Roy R, Edgerton VR. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol. 2002;157:571–577. doi: 10.1083/jcb.200112106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, Thomas K, Austin T, Edwards C, Cuzzourt J, Duenzl M, Lucas PA, Black AC., Jr Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec. 2001;264:51–62. doi: 10.1002/ar.1128. [DOI] [PubMed] [Google Scholar]
  8. Asakura A, Seale P, Girgis-Gabardo A, Rudnicki MA. Myogenic specification of side population cells in skeletal muscle. J Cell Biol. 2002;159:123–134. doi: 10.1083/jcb.200202092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Zammit P, Beauchamp J. The skeletal muscle satellite cell: stem cell or son of stem cell? Differentiation. 2001;68:193–204. doi: 10.1046/j.1432-0436.2001.680407.x. [DOI] [PubMed] [Google Scholar]
  10. Tamaki T, Akatsuka A, Yoshimura S, Roy RR, Edgerton VR. New fiber formation in the interstitial spaces of rat skeletal muscle during postnatal growth. J Histochem Cytochem. 2002;50:1097–1111. doi: 10.1177/002215540205000812. [DOI] [PubMed] [Google Scholar]
  11. Okabe M, Ikawa M, Kominami K, Nakanishi T, Nishimune Y. ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett. 1997;407:313–319. doi: 10.1016/s0014-5793(97)00313-x. [DOI] [PubMed] [Google Scholar]
  12. Fukada S, Miyagoe-Suzuki Y, Tsukihara H, Yuasa K, Higuchi S, Ono S, Tsujikawa K, Takeda S, Yamamoto H. Muscle regeneration by reconstitution with bone marrow or fetal liver cells from green fluorescent protein-gene transgenic mice. J Cell Sci. 2002;115:1285–1293. doi: 10.1242/jcs.115.6.1285. [DOI] [PubMed] [Google Scholar]
  13. LaBarge MA, Blau HM. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell. 2002;111:589–601. doi: 10.1016/s0092-8674(02)01078-4. [DOI] [PubMed] [Google Scholar]
  14. Osawa M, Nakamura K, Nishi N, Takahasi N, Tokuomoto Y, Inoue H, Nakauchi H. In vivo self-renewal of c-Kit+ Sca-1+ Lin(low/−) hemopoietic stem cells. J Immunol. 1996;156:3207–3214. [PubMed] [Google Scholar]
  15. Jackson KA, Mi T, Goodell MA. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci USA. 1999;96:14482–14486. doi: 10.1073/pnas.96.25.14482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Qu-Petersen Z, Deasy B, Jankowski R, Ikezawa M, Cummins J, Pruchnic R, Mytinger J, Cao B, Gates C, Wernig A, Huard J. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J Cell Biol. 2002;157:851–864. doi: 10.1083/jcb.200108150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McKinney-Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA. Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci USA. 2002;99:1341–1346. doi: 10.1073/pnas.032438799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Torrente Y, Tremblay JP, Pisati F, Belicchi M, Rossi B, Sironi M, Fortunato F, El Fahime M, D’Angelo MG, Caron NJ, Constantin G, Paulin D, Scarlato G, Bresolin N. Intraarterial injection of muscle-derived CD34(+)Sca-1(+) stem cells restores dystrophin in mdx mice. J Cell Biol. 2001;152:335–348. doi: 10.1083/jcb.152.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Beauchamp JR, Heslop L, Yu DS, Tajbakhsh S, Kelly RG, Wernig A, Buckingham ME, Partridge TA, Zammit PS. Expression of CD34 and myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J Cell Biol. 2000;151:1221–1234. doi: 10.1083/jcb.151.6.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lee JY, Qu-Petersen Z, Cao B, Kimura S, Jankowski R, Cummins J, Usas A, Gates C, Robbins P, Wernig A, Huard J. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J Cell Biol. 2000;150:1085–1100. doi: 10.1083/jcb.150.5.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakamura Y, Ando K, Chargui J, Kawada H, Sato T, Tsuji T, Hotta T, Kato S. Ex vivo generation of CD34(+) cells from CD34(−) hematopoietic cells. Blood. 1999;94:4053–4059. [PubMed] [Google Scholar]
  22. Sato T, Laver JH, Ogawa M. Reversible expression of CD34 by murine hematopoietic stem cells. Blood. 1999;94:2548–2554. [PubMed] [Google Scholar]
  23. Smith HK, Maxwell L, Rodgers CD, McKee NH, Plyley MJ. Exercise-enhanced satellite cell proliferation and new myonuclear accretion in rat skeletal muscle. J Appl Physiol. 2001;90:1407–1414. doi: 10.1152/jappl.2001.90.4.1407. [DOI] [PubMed] [Google Scholar]
  24. Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci USA. 2003;100:2088–2093. doi: 10.1073/pnas.0337659100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells. 2001;19:180–192. doi: 10.1634/stemcells.19-3-180. [DOI] [PubMed] [Google Scholar]
  26. Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, Von Moers A, Morris GE, Den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J Clin Invest. 2002;110:807–814. doi: 10.1172/JCI16098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ratajczak M, Majka M, Kucia M, Drukala J, Pietrzkowski Z, Peiper S, Janowska-Wieczorek A. Expression of functional CXCR4 by muscle satellite cells and secretion of SDF1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and haematopoietic stem/progenitor cells in muscles. Stem Cells. 2003;21:363–371. doi: 10.1634/stemcells.21-3-363. [DOI] [PubMed] [Google Scholar]
  28. Torrente Y, Camirand G, Pisati F, Belicchi M, Rossi B, Colombo F, El Fahime M, Caron NJ, Issekutz AC, Constantin G, Tremblay JP, Bresolin N. Identification of a putative pathway for the muscle homing of stem cells in a muscular dystrophy model. J Cell Biol. 2003;162:511–520. doi: 10.1083/jcb.200210006. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES