Mesenchymal stem cells for cartilage regeneration in dogs

Table 1 Surface marker expression in canine mesenchymal stem cells

Source	Positive marker	Negative marker	Ref.
Adipose tissue	CD90, CD44, CD73, CD105	CD45, CD34, CD14	Kang et al[50], 2012
Bone marrow	CD90, CD44, CD73, CD105	CD45, CD34, CD14
Umbilical cord	CD90, CD44, CD73, CD105	CD45, CD34, CD14
Wharton's jelly	CD90, CD44, CD73, CD105	CD45, CD34, CD14
Adipose tissue	CD90, CD44	CD45, CD34, CD146	Kisiel et al[52], 2012
Bone marrow	CD90, CD44	CD45, CD34, CD146
Muscle	CD90, CD44	CD45, CD34, CD146
Periosteum	CD90, CD44	CD45, CD34, CD146
Adipose tissue	CD90, CD44	CD45, CD11b	Sasaki et al[40], 2018
Bone marrow	CD90, CD44	CD45, CD11b
Synovium	CD90, CD44	CD45, CD11b
Infrapatellar fat pad	CD90, CD44	CD45, CD11b
Adipose tissue	CD90, CD44, CD105, CD9	CD45, CD34, Stro-1	Bearden et al[53], 2017
Bone marrow	CD90, CD44, CD105, CD9	CD45, CD34, Stro-1
Synovium	CD90, CD44, CD105, CD9	CD45, CD34, Stro-1
Adipose tissue	CD90	-	Reich et al[56], 2012
Bone marrow	CD90	-
Adipose tissue	CD90, CD44, CD29	CD45, CD34	Takemitsu et al[64], 2012
Bone marrow	CD90, CD44, CD29	CD45, CD34
Adipose tissue	CD90, CD44, MHCI	CD34, CD29, CD14, MHCII	Screven et al[49], 2014
Bone marrow	CD90, CD44, MHCI	CD34, CD29, CD14, MHCII
Adipose tissue	CD90, CD44	CD45, CD34, CD14	Sullivan et al[118], 2016
Bone marrow	CD90, CD44	CD45, CD34, CD14
Adipose tissue	CD90, CD44, CD29, CD73, CD4, CD8, MHCI	CD45, CD34, CD14, MHCII	Russell et al[57], 2016
Bone marrow	CD90, CD44, CD29, CD73, CD4, CD8, MHCI	CD45, CD34, CD14, MHCII
Adipose tissue	CD90, CD44, MHCI	CD45, CD34, CD14, CD3, CD4, CD8, CD172a, CD11c, HLA-DR, sIgM	Kang et al[62], 2008
Adipose tissue	CD90, CD44, CD29	CD45, CD34, CD14, CD117, CD13 CD105, CD73	Vieira et al[48], 2010
Adipose tissue	CD90, CD44, CD140, CD117	CD45, CD34	Martinello et al[65], 2011
Bone marrow	CD90, MHCI	CD45, CD34, MHCII	Kamishina et al[119], 2006
Bone marrow	CD90, CD105	CD45, CD34	Csaki et al[46], 2007
Bone marrow	CD44, Stro-1	CD45, CD34	Hodgkiss-Geere et al[120], 2012
Bone marrow	CD90, CD44	CD14	Bertolo et al[73], 2015
Bone marrow	CD90, CD44, CD105, CD73, CD166, vimentin	CD31	Zhang et al[47], 2018
Bone marrow	CD90, CD44, CD29, CD105, CD166	CD45, CD34	Li et al[63], 2018
Synovium	CD90, CD44	-	Wijekoon et al[54], 2017
Synovial fluid	CD90	CD45, CD34	Krawetz et al[55], 2012

Table 2 Surface marker expression in canine mesenchymal stem cells

Source	Differentiation potential	Ref.
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis	Csaki et al[46], 2007
Adipose tissue	Adipogenesis, osteogenesis, neurogenesis	Kang et al[62], 2008
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis	Neupane et al[68], 2008
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis, myogenesis	Vieira et al[48], 2010
Adipose tissue	Adipogenesis, osteogenesis, myogenesis	Martinello et al[65], 2011
Adipose tissue	Chondrogenesis	Reich et al[56], 2012
Bone marrow
Adipose tissue	Osteogenesis	Kang et al[50], 2012
Bone marrow
Umbilical cord
Wharton's jelly
Adipose tissue	Adipogenesis, osteogenesis	Kisiel et al[52], 2012
Bone marrow
Muscle
Periosteum
Adipose tissue	Adipogenesis, osteogenesis	Takemitsu et al[64], 2012
Bone marrow
Bone marrow	Chondrogenesis, cardiogenesis	Hodgkiss-Geere et al[120], 2012
Synovial fluid	Chondrogenesis	Krawetz et al[55], 2012
Bone marrow	Adipogenesis, osteogenesis, chondrogenesis	Volk et al[59], 2012
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis	Guercio et al[58], 2013
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis	Screven et al[49], 2014
Bone marrow
Bone marrow	Adipogenesis, osteogenesis, chondrogenesis	Bertolo et al[60], 2015
Adipose tissue	Osteogenesis, chondrogenesis	Sullivan et al[118], 2016
Bone marrow
Adipose tissue	Adipogenesis, osteogenesis	Russell et al[57], 2016
Bone marrow
Synovium	Adipogenesis, osteogenesis, chondrogenesis, osteoclast differentiation	Wijekoon et al[54], 2017
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis	Bearden et al[53], 2017
Bone marrow
Synovium
Bone marrow	Adipogenesis, osteogenesis, chondrogenesis Hepatocyte and functional insulin-secreting cell differentiation	Zhang et al[47], 2018
Adipose tissue	Adipogenesis, osteogenesis, chondrogenesis	Sasaki et al[40], 2018
Bone marrow
Synovium
Infrapatellar fat pad
Bone marrow	Chondrogenesis	Endo et al[61], 2018

Table 3  In vivo study of canine mesenchymal stem cells for cartilage repair

Source	Injection / trans-plantation	Combination use	Cell number (million)	Model	Evaluation method	Ref.
Bone marrow	Single intraarticular, autologous	-	7-8	Partial thickness articular cartilage defect	Histology	El-Tookhy et al[86], 2008
Adipose tissue	Single intraarticular, autologous	-	7-8	Partial thickness articular cartilage defect	Morphology, histology, fluorescence analysis	Mokbel et al[87], 2011
Adipose tissue	Four times intraarticular, allogeneic	-	5 (three times), 66 (once)	Intact	Pain and lameness scoring, immunohistochemistry	Park et al[95], 2013
Bone marrow	Transplantation with scaffold, allogeneic	Scaffold	0.01	Full-thickness cartilage defect	Histology, immunohistochemistry, micro CT	Duan et al[89], 2013
Synovium	Single intraarticular, autologous	Hyaluronic acid	0.05, 5 or 50	Partial thickness articular cartilage defect	Histology	Miki et al[88], 2015
Adipose tissue	Single intraarticular, allogeneic	Platelet-rich plasma	10	Cranial cruciate ligament transection	Lameness scoring, focal compression strength, extracellular matrix composition, histopathology, real-time PCR	Yun et al[90], 2016
Bone marrow	Single intraarticular, allogeneic	Hyaluronic acid	10	Partial thickness articular cartilage defect	Gross appearance, magnetic resonance imaging, histology, immunohistochemistry	Li et al[63], 2018
Umbilical cord	Single intraarticular, allogeneic	-	1	Surgical manipulation of articular cartilage	Magnetic resonance imaging, radiography, ultrasonography, blood test, scanning electron microscope	Zhang et al[51], 2018

Table 4 Clinical study of canine mesenchymal stem cells for osteoarthritis in dogs

Source	Injection	Cell number (million)	Target joint	Observation period	Evaluation points	Ref.
Adipose tissue	Single intraarticular, autologous	4.2-5	Hip	30, 60, 90 d	Lameness, pain, range of motion, functional disability, owner questionnaire	Black et al[121], 2007
Adipose tissue	Single intraarticular, autologous	3-5	Elbow	30, 60, 90, 180 d	Lameness, pain, range of motion, functional disability, owner questionnaire	Black et al[107], 2008
Adipose tissue	Single intraarticular with platelet-rich plasma or hyaluronic acid, autologous	3-5	Elbow	1 wk, 1 mo	Not described	Guercio et al[103], 2012
Adipose tissue	Single intraarticular with platelet-rich plasma, autologous	Over 30	Hip	0, 30, 90, 180 d	Gait analysis	Vilar et al[104], 2013
Adipose tissue	Single intraarticular, autologous	30	Hip	1, 3, 6 mo	Pain, functional disability, range of motion, owner questionnaire	Cuervo et al[122], 2014
Adipose tissue	Single intraarticular, autologous	15	Hip	0, 30, 90, 180 d	Gait analysis	Vilar et al[108], 2014
Adipose tissue	Acupoint injection, allogeneic	0.2-0.8	Hip	7, 15, 30 d	Pain, functional disability, range of motion	Marx et al[106], 2014
Adipose tissue	Single intraarticular, allogeneic	12	Hip, elbow, stifle, shoulder	60 d	Pain, owner questionnaire	Harman et al[123], 2016
Bone marrow	Single intraarticular and single intravenous, autologous	5 for intraarticular, 2 for intravenous	Stifle	4, 8 wk	Circulating T lymphocyte, C reactive protein and cytokine concentration, total cell count in synovial fluid	Muir et al[110], 2016
Adipose tissue	Single intraarticular with hyaluronic acid, allogeneic	12	Elbow	6, 9, 12 mo	Owner questionnaire, arthroscopic image, histology	Kriston-Pál et al[105], 2017
Adipose tissue	Single intraarticular and/or single intravenous, allogeneic	Not described	Various joints	10 wk	Lameness, pain, range of motion, functional disability	Shah et al[124], 2018