Optimizing mesenchymal stem cell therapy for tendon-bone healing: Multifaceted approaches and future directions

Table 1 Summary of the effects of preconditioning methods on stem cells

Ref.	Pretreatment method	Cell type	Effects on stem cells	Mechanism	Animal model
Song et al[21], 2017	Mechanical stimulation	Rabbit BMSCs	Promote proliferation and differentiation	Increase collagen I, collagen III, ALP, OPN, tenascin C, and tenomodulin expression	Rabbit ACLR model
Wang et al[20], 2023	Mechanical stimulation	Mouse BMSCs	Promote chondrogenic differentiation	Stimulate macrophage polarization towards the M2 phenotype and secretion of TGF-β1	Mouse ACLR model
Li et al[17], 2015	Mechanical stimulation	Rat BMSCs	Inhibit adipogenic differentiation	Activate the TGFβ1/Smad2 signaling pathway	N/A
Kusuyama et al[26], 2014	LIPUS	Mouse MSCs line	Inhibit adipogenic differentiation, promote osteogenic differentiation	Regulate the ROCK-Cot/Tpl2-MEK-ERK signaling pathway and PPARγ2 activity	N/A
Chen et al[27], 2023	LIPUS	hUC-MSCs	Promote chondrogenic differentiation	Inhibit the TNF signaling pathway	Rat cartilage defect model
Wang et al[28], 2019	LIPUS	Rat BMSCs	Promote chondrogenic differentiation	Inhibit autophagy	N/A
Zhao et al[29], 2021	ESW	Human SCB-SPCs	Promote self-renewal	Activate the YAP/TAZ signaling pathway	Rabbit osteochondral defect model
Chen et al[31], 2017	ESW	Rat BMSCs	Promote proliferation and osteogenic differentiation	Increase Col1, OSX, Runx2, and ALP expression	Rat femoral shaft bone defect model
Hu et al[32], 2016	ESW	Human BMSCs, TDSCs, ADSCs	Promote osteogenic differentiation	Inhibit miR-138 to activate the FAK-ERK1/2-RUNX2 signaling pathway	Nude mouse bone induction model
Catalano et al[33], 2017	ESW	Human ADSCs	Promote osteogenic differentiation	Activate the ROS-ERK1/2-BMP2-Smad-RUNX2 signaling pathway	N/A
Wu et al[37], 2022	SLPI	Rat BMSCs	Promote migration and osteogenic differentiation	Upregulate Runx2, ALP, OCN, and OPN gene expression	Rat ACLR model
Han et al[38], 2024	TFRD	Mouse BMSCs	Promote vitality and osteogenic differentiation	Activate ERR1/2-Gga1-TGF-β/MAPK pathway	Rat ACLR model
Zhang et al[39], 2017	PVP-I	Rabbit BMSCs	Promote osteogenic differentiation	Increase the expression of BMP-2 and OPN	Rabbit ACLR model
Tian et al[40], 2018	Baicalein	Rat TDSCs	Promote osteogenic differentiation	Activate the Wnt/β-catenin signaling pathway	Rat calcaneus-Achilles tendon injury model
Wang et al[41], 2016	Icariin	Mouse MSCs	Promote osteogenic differentiation	Activate the Wnt/β-catenin signaling pathway	Mouse calvarial osteolysis model
Alipanah-Moghadam et al[42], 2023	Andrographolide	Rat BMSCs	Increase cell resistance to environmental stress	Induce the expression of HO-1	N/A
Tie et al[43], 2021	Dedifferentiated	Rabbit BMSCs	Promote osteogenic differentiation	Activate the Nanog/NFATc1/OSX signaling pathway	Rabbit ACLR model
Díaz-Tocados et al[44], 2017	Mg2+	Rat BMSCs	Promote proliferation and osteogenic differentiation	Activate the Notch1 signaling pathway	Rat femur decellularized scaffold
Kim et al[45], 2015	Static magnetic fields	Human BMSCs	Promote proliferation and osteogenic differentiation	Upregulate ALP, BSP-2, COL1A1, OCN, ON, OPN, OSX, and RUNX2 gene expression	N/A

BMSC: Bone marrow-derived stem cell; ALP: Alkaline phosphatase; OPN: Osteopontin; ACLR: Anterior cruciate ligament reconstruction; TGF: Transforming growth factor; LIPUS: Low-intensity pulsed ultrasound; MSC: Mesenchymal stem cell; ROCK: Rho-associated kinase; Cot/Tpl2: Cancer Osaka thyroid oncogene/tumor progression locus 2 kinase; MEK: Mitogen-activated protein kinase kinase 1; FAK: Focal adhesion kinase; ERK: Extracellular signal-regulated kinase; PPARγ2: Peroxisome proliferator-activated receptor gamma 2; hUC-MSC: Human umbilical cord-derived mesenchymal stem cell; TNF: Tumor necrosis factor; ESW: Extracorporeal shock wave; SCB-SPCs: Subchondral bone stem/progenitor cells; YAP: Yes-associated protein; TAZ: Transcriptional co-activator with PDZ-binding motif; Col1: Type I collagen; NFATc1: Nuclear factor of activated T-cells 1; OSX: Osterix; Runx2: Runt-related transcription factor 2; TDSC: Tendon-derived stem cell; ADSC: Adipose-derived stem cell; ROS: Reactive oxygen species; BMP2: Bone morphogenetic protein 2; OCN: Osteocalcin; SLPI: Secretory leukocyte protease inhibitor; TFRD: Total flavonoids of Rhizoma Drynariae; ERR1/2: Estrogen-related receptor 1 and 2; Gga1: Golgi-localized γ-ear containing ADP ribosylation factor-binding protein 1; MAPK: Mitogen-activated protein kinases; PVP-I: Polyvinylpyrrolidone iodine; HO-1: Heme oxygenase-1; BSP-2: Bone sialoprotein-2; COL1A1: Collagen type 1 alpha 1; ON: Osteonectin; N/A: Not available.