The Application of Stem Cells from Different Tissues to Cartilage Repair
Table 1
Summary of recent results in the application of stem and progenitor cells to cartilage repair and regeneration.
(a)
Author
Year
Cell source
Model
Experimental study
Adverse effects
Key findings
Shafiee et al.
2011
Cartilage
Mice
Proliferation, tumourigenesis, and multipotency of nasal septum-derived adult cells
None
NCs retained chondrogenic potential until passage 35. Markers suggest chondrogenic ability equal to that of BMSCs
do Amaral et al.
2012
Cartilage
In vitro
Proliferation and multipotency of nasal septal cartilage surface zone cells within the context of cartilage repair
NA
Cells in pellet culture resulted in chondrogenesis without TGF-β or BMPs. NCs were CD105+, CD73+, CD44+, and CD146−
Pelttari et al.
2014
Cartilage
Humans (10), mice, goats
Suitability of adult human neuroectoderm-derived nasal chondrocytes for articular cartilage repair
None
NCs proliferated faster and were more chondrogenic than Acs in vitro. In vivo, defect filling was observed after 4 months
Jiang et al.
2016
Cartilage
Humans (15), mice
Cartilage repair potential of resident cartilage stem/progenitor cells
None
ACs became CD146+ in high-density 2D culture, and their chondrogenic potential is similar to that of BMSCs. In vivo results were promising
Embree et al.
2016
Cartilage
Rats, rabbits
Potential of single resident fibrocartilage stem cells (FCSC) to regenerate cartilage, bone, and haematopoietic compartment
None
FCSCs spontaneously produced cartilage anlage in vivo which was then remodeled into trabecular bone. Addition of sclerostin maintained the FCSC pool and led to chondrocyte differentiation and cartilage repair in vivo
Fellows et al.
2017
Cartilage
In vitro
Senescence of healthy versus diseased human knee articular cartilage rather than regenerative potential per se
NA
The number of progenitor cells was greater (2x, ) in OA tissue than in healthy cartilage. Subpopulation of OA-derived cells had reduced proliferative potential and underwent early senescence in vitro. An increase in senescent cells may contribute to the disease phenotype
Pittenger et al.
1999
BM
In vitro
Maintenance of multipotency in individual adult BMSCs
NA
Adult stem cells can be induced to differentiate exclusively into adipocytic, chondrocytic, and osteogenic lineages
Wakitani et al.
2004
BM
Humans (2)
Effectiveness of autologous BMSC transplantation for the repair of full-thickness articular cartilage defects in the patellae of 2 individuals
None
Clinical symptoms (pain & walking impediment) were significantly reduced 6 months postop. Benefits remained for 4-5 years. Arthroscopy revealed defects filled with fibrocartilage
Wakitani et al.
2011
BM
Humans (41)
Safety of autologous BMSC implantation for cartilage defects
None
No tumour or infections reported in any patient. Five had total knee replacement due to progression to OA
Wong et al.
2013
BM
Humans (56)
Autologous BMSC i.a. injections with microfracture and tibial osteotomy
None
The experimental group showed significantly better IKDC (), Tegner (), MOCART (), and Lysholm () scores
(b)
Author
Year
Cell source
Model
What was examined
Adverse effects
Key findings
Vangsness et al.
2014
BM
Humans (55)
Safety and effects on OA changes in the knee following intra-articular injection of allogeneic human BMSCs
None
Evidence of meniscus regeneration and improvement in knee pain following treatment with allogeneic human mesenchymal stem cells
Gobbi et al.
2014
BM
Humans (25)
BMAC (BM aspirate concentrate) for the repair of large full-thickness knee cartilage defects
None
Significant improvement in Tegner, Marx, Lysholm, VAS, IKDC subjective, and KOOS scores at the final follow-up compared with their respective preoperative scores (); MRI analysis at the final follow-up showed stable implantation and complete filling of the defect in 20 of 25 patients
Vega et al.
2015
BM
Humans (30)
Effects of i.a. injection of allogeneic BMSC versus hyaluronic acid for the treatment of knee OA
None
At 1-year follow-up, cartilage formation in cell-treated defects was significantly improved over control (HA)-treated defects
Nakagawa et al.
2016
BM
Rats
Lubricin expression and chondrogenesis in BMSCs using pellets & hanging-drop cultures in vitro and in vivo
NS
The treatment group scored significantly higher than the control group when assessed histologically at 8 and 12 weeks
Chen et al.
2016
BM
Rabbits
PTH-treated versus untreated BMSCs embedded in fibrin glue for the repair of induced articular cartilage injury in rabbits
None
The ICRS score significantly increased () in PTH-treated versus non-PTH and untreated groups. Significantly increased levels of type II collagen and aggrecan mRNA and protein in PTH versus non-PTH groups ()
Shapiro et al.
2017
BM
Humans (25)
BMAC for the treatment of knee pain from bilateral osteoarthritis
None
Knee pain decreased in all groups, although no significant difference between BMAC and saline groups ()
Koga et al.
2008
Synovium
Rabbits
“Local adherent technique” whereby an i.a. injection of synovium stem/progenitor cells adheres to the defect site within 10 minutes
NA
Increased cell attachment correlated with improved cartilage repair at 24 weeks. It was reported that 60% of injected cells adhered at the site
Nakamura et al.
2012
Synovium
Pigs
Adherence of synovium-derived cells to cartilage defects and effects on cartilage
None
The cartilage matrix detected in all treated defects versus none in the control group. Wakitani and ICRS scores were significantly higher in treatment groups (). Higher chondrogenic potential in synovial cells versus BM, adipose, muscle, or periosteum-derived cells
Sekiya et al.
2015
Synovium
Humans (10)
“Local adherent technique” using autologous synovium-derived stem/progenitor cells
1 patient had fibrillation of repaired cartilage
Transplantation of synovial cells was deemed effective: Lysholm and MRI-based scores increased over 3 years + follow-up period (both )
Mak et al.
2016
Synovium
Mice
Chondrogenic potential of synovium-derived sca-1-positive stem/progenitor cells injected into injured joint
NS
Intra-articular injection of Sca-1+ GFP+ synovial cells from C57BL6 or MRL/MpJ “super-healer” mice to C57BL6 mice following cartilage injury led to similar levels of cartilage repair. Treatment with cells resulted in cartilage repair that was significantly greater than that of untreated defects
Baboolal et al.
2016
Synovium
Dogs
Role of HA on MSC attachment to cartilage
NS
It was confirmed that HA inhibits MSC-cartilage attachment
Diekman et al.
2010
Adipose
In vitro
Differences in chondrogenic potential of ADSC and BMSC in different culture conditions
NA
ADSCs and BMSCs require different in vitro culture conditions to achieve optimal chondrogenic outcomes. While both ADSC and BMSC underwent chondrogenic differentiation in all conditions tested, BMSCs produced a more matrix over a wider range of conditions
Koh et al.
2013
Adipose
Humans (18)
Outcome of i.a. injections of autologous ADSCs for the treatment of knee OA
One case of pain and swelling
Significant reduction in WOMAC scores () relative to preop levels. The Lysholm score increased from 40.1 points to 73.4 points (), and the mean VAS score decreased over the period of the study from 4.8 to 2.0 ()
Jo et al.
2014
Adipose
Humans (18)
Safety and efficacy of i.a. injections of autologous ADSC for knee OA
None
Improvements were seen in the high-dose group (improvement in WOMAC & VAS at 6 months). Significant decreases in cartilage defect size paralleled by an increase in cartilage volume at some defect sites at 6 months
Koh et al.
2015
Adipose
Humans (30)
Injection of ADSCs and arthroscopic lavage for knee OA
Slight knee pain, resolved with medication
The technique appears to be effective in cartilage healing, reducing pain, and improving function
Koh et al.
2016
Adipose
Humans (80)
ADSCs with fibrin glue and microfracture (MFX) versus MFX alone in patients with symptomatic knee cartilage defects
NS
Both treatment groups saw improvement in multiple clinical outcomes; however, the degree of improvement was greater in patients who received ADSC in addition to MFX
Pers et al.
2017
Adipose
Humans (18)
Intra-articular injections of different doses of ADSCs
Unstable angina pectoris reported in 1 patient, 5 minor AEs reported by four patients potentially related to the procedure
All dose groups saw an overall negative trend in WOMAC (pain, stiffness, and function), VAS, and SAS, although these data were significant only in the low-dose group
Saw et al.
2013
Peripheral blood
Humans (50)
Postoperative i.a. injections of hyaluronic acid with and without PBSC
None
A nonsignificant () increase in the IKDC score for the PBSC group at 24 months. A significant () increase in the MRI score in the PBSC group at 18 months
Fu et al.
2014
Peripheral blood
Rabbits
Mobilised rabbit PBSCs versus rabbit BMSCs for in vivo chondrogenesis
None
PBSCs showed greater chondrogenic potential than BMSCs in vitro, although both cell types performed equally well in in vivo assays for cartilage repair
Fu et al.
2014
Peripheral blood
Humans (1)
Injection of autologous activated PBSCs + autologous periosteum flap in a chondral lesion
None
Second-look arthroscopy showed a smooth surface at 8 months postoperation. CT and MRI evaluations showed a significant improvement compared to preoperation
Saw et al.
2015
Peripheral blood
Humans (8)
Autologous PBSCs and HA with concomitant medial open-wedge high tibial osteotomy
None
At 25-month follow-up, arthroscopy and biopsy revealed smooth, well-integrated regenerated tissue rich in type II collagen and proteoglycan, with some type I collagen present
Ha et al.
2015
Umbilical cord
Minipigs
Ability of human UBSC cell lines in HA hydrogel (versus empty defects) to repair osteochondral defects
None
Defects which received cells + HA had more safranin-O-positive staining, more regenerated cartilage, and better integration with the surrounding tissue. The IRCS score was better in cell transplant defects than in empty defects
Li et al.
2016
Umbilical cord
In vitro
It was determined whether coculture of human ACs could increase chondrogenic potential of human UBSCs
NA
Indirect coculture increased expression of chondrogenic markers. However, qPCR, WB, and some 2D IHC data contain inconsistencies
Gomez-Leduc et al.
2016
Umbilical cord
Mice
Chondrogenic potential of human UCBSCs seeded on type I/III collagen sponges ± chondrogenic factors
NS
UBSCs cultured in vitro with TGF-β1 and BMP-2 were implanted in nude mice. Cells exposed to growth factors in an in vitro phase produced a cartilaginous matrix rich in type II collagen. No scaffolds progressed to calcification but instead deposited type II collagen-rich ECM
Park et al.
2017
Umbilical cord
Humans (1)
Transplanted human UCBSCs in a 4% HA hydrogel into a rabbit trochlea defect
None
VAS, IKDC, & WOMAC improved. At 1-year follow-up, second-look arthroscopy and biopsy showed smooth safranin-O-positive hyaline-cartilage with excellent peripheral integration. MRI showed defect filling, abundant repair tissue, and good integration with the surrounding tissue
Park et al.
2017
Umbilical cord
Humans (7)
Treatment of a large osteochondral defect by autologous UCBSCs in a HA hydrogel
None
Regenerated tissue was thick, smooth, and glossy white with good integration with the surrounding tissue and resembled hyaline-like cartilage with abundant GAG content. No bone formation or overgrowth was observed
Park et al.
2017
Umbilical cord
Rabbits
Efficacy of human autologous UCBSCs and HA hydrogels for cartilage regeneration
None
Macroscopically, cells + hydrogel produced better cartilage formation than hydrogel only or untreated controls. Regenerated tissue was smooth and type II collagen rich
