Cell-Based Therapies for the Treatment of Shoulder and Elbow Tendinopathies: A Scoping Review

Table 1

Synopsis of clinical studies dealing with cell-based approaches in rotator cuff pathology.

Publication	Level of evidence	Modified Coleman score	Pathology	of patients	Therapeutic protocol	MSC manipulation	Outcomes and imaging	Follow-up	Results
WITH ROTATOR CUFF SURGICAL REPAIR
Ellera Gomes et al., KSSTA [20]	IV case series	58	Full-thickness tear	14	Transosseous mini form post iliac crest (same time of surgery)	100 ml of bone marrow: MSC fractions were obtained according to good manufacturing practices by Ficoll–Hypaque density gradient and then resuspended in saline solution enriched with 10% autologous serum to a final volume of 10 ml		12 months	(i) Good functional results; (ii) Tendon integrity in all cases at 12 months MRI with some signal artifacts which did not affect the final functional result; (iii) 1 failure
Hernigou et al., Int Orthop.[18]	III case control study	64	Full-thickness supraspinatus tear (1.5–2.5 cm)	90 (45 with and 45 without ASC)	Arthroscopic single-row repair with suture anchors with or without BMAC from anterior iliac crest (same time of surgery)	150 ml of bone marrow aspirate concentrated in the cellular and molecular therapy laboratory	US (every month), MRI (3 months, 6 months, 1 year, 2 years, and last minimum 10 years)	Minimum 10 years	(i) MSCs improved the healing rate at 6 months and decreases the retear rate at 10 years; (ii) The number of MSCs correlated to the grade of healing
Kim et al., AJSM [19]	III cohort study	63	Full-thickness RCT	70 (35 with and 35 without ASC)	Arthroscopic double-row repair with or without a-dMSC (from the glue scaffold (liposuction one day before arthroscopy)	Liposuction of 120 ml of adipose tissue: MSC lab. isolation and preparation followed by injection with fibrin glue scaffold—Greenplast kit (Green Cross)	VAS, CS, UCLA, and (minimum 1 year)	Minimum 24 months	(i) No significant functional difference; (ii) Significantly lower retear rate with MSCs
WITHOUT ROTATOR CUFF SURGICAL REPAIR
Centeno et al., Journal of Pain Research [23]	IV case series	52	G-H OA and/or partial or full-thickness tear	Uncontrolled treatment registry population: 115 (81 RCT and 34 OA); available follow-up for 40 (DASH) and 55 (NPS)	BMAC from post iliac and PL injection (+hypertonic dextrose solution injection 2 or 5 days before) intra-articular or in the RCT	BMAC centrifugation followed by addition of PRP and PL	DASH, NPS	3 and 24 months	(i) Significant improvement of DASH and pain (NPS); (ii) No differences between OA and rotator cuff groups
Kim et al., Cell Transplantation [22]	IV case series	47	Partial thickness tear	12	BMAC from iliac injection at the tear site (US guidance)	BMAC centrifugation with BIOMET MarrowStim™ mini kit followed by injection of 2 ml of BMACs mixed with 1 ml of PRP	ASES,	3 months	(i) Significant improvement of VAS and ASES; (ii) Reduction of the tear size but the change was not statistically significant
Kim et al., JOSR [21]	III case control study	49	Partial thickness tear	24 (12 BMAC-PRP vs 12 rehabilitation)	BMAC from iliac injection at the tear site (US guidance)	BMAC centrifugation with BIOMET MarrowStim™ mini kit followed by injection of 2 ml of BMACs mixed with 1 ml of PRP	ASES,	3 months	(i) Significantly higher VAS and ASES in the BMAC-PRP group; (ii) The change in the tear size did not differ significantly between groups; (iii) Manual muscle test and use of medications were not significantly different between the two groups
Jo et al., Stem Cells [24]	IV case series	48	Partial thickness tear	18 (3 low, 3 mid, and 3 high dose for safety review and then the other 9 pts are high dose)	Injection of a-dMSC (from abdomen) (liposuction 3 weeks before injections)	Cells from stromal vascular fraction isolated and cultured in keratinocyte-SFM- (Invitrogen) based media containing 0.2 mM ascorbic acid, 0.09 mM calcium, 5 ng/ml recombinant epidermal growth factor, and 5% fetal bovine serum	SPADI, CS, (1 month, 3 months, and 6 examination	6 months	(i) No serious adverse event; (ii) SPADI and CS significantly improved in mid- and high-dose groups; (iii) VAS significantly alleviated by 71% in the high-dose group; (iv) Bursal side defect significantly decreased by 90% in the high-dose group at MRI examination; (v) Articular and bursal side defects decreased by 83% and 90% in the mid- and high-dose groups at arthroscopic examination

RCT: rotator cuff tear; G-H OA: gleno-humeral osteoarthritis; BMAC: bone marrow aspirate concentrate; MSC: mesenchymal stem cells; a-dMSC: adipose-derived mesenchymal stem cells; PRP: platelet-rich plasma; PL: platelet lysate; VAS: visual analogue scale; NPS: numeric pain scale; CS: Constant-Murley Score; ASES: American Shoulder and Elbow Surgeons; UCLA: University of California, Los Angeles; DASH: shoulder and hand score; SPADI: Pain And Disability Index; ROM: range of motion; MRI: magnetic resonance imaging; US: ultrasound.