Is cellular therapy beneficial in management of rotator cuff tears? Meta-analysis of comparative clinical studies

Table 1 Characteristics of included studies (n = 6)

No.	First author	Year	Country	Study design	Sample size	Cases/controls	MSC source	PRP	Cellular dosage (106 cells)	Comparator intervention	Case age (SD)	Control age (SD)	Case male: Female	Control male: Female	Follow-up timeline (mo)
1	P Hernigou	2014	France	RCS	90	45/45	BM-MSC	No	0.051	Surgery	61 ± 4.5	61 ± 4.5	21:24	20:25	6, 120
2	YS Kim	2017	Korea	RCS	70	35/35	AD-MSC	No	4.46	Surgery	59.2 ± 3.4	57.6 ± 2.9	15:20	13:22	28.3
3	SJ Kim	2018	Korea	PCS	24	12/12	BM-MSC	Yes	1	Exercise therapy	54.9 ± 7.6	59.6 ± 7.2	05:07	08:04	0.7, 3
4	JR Lamas	2019	Spain	RCT	13	8/5	BM-MSC	No	20	Surgery	57.8 ± 6.5	61.8 ± 3.8	06:02	02:03	12
5	C Centeno	2020	USA	RCT	25	14/11	BM-MSC	Yes	810	Exercise therapy	46 ± 11	49 ± 11	09:05	05:06	1, 12
6	JL Hurd	2020	USA	RCT	16	11/5	AD-MSC	No	11.4	Steroid	64.6 ± 9.6	57.6 ± 6.2	08:03	05:00	6, 12

AD: Adipose derived; BM: Bone marrow derived; MSC: Mesenchymal stem cell; PCS: Prospective controlled study; RCS: Retrospective comparative study; RCT: Randomized controlled trial; SD: Standard deviation; USA: United States of America.

Table 2 Biological treatment protocol of the included studies (n = 6)

Ref.	MSC type	MSC source	Rotator cuff tear nature	Preparation method	Cellular dosage (106 cells)	Treatment group intervention	Control group intervention	Outcome measures
Hernigou et al[11]	BM-MSC	Auto	Full thickness	150 mL of bone marrow aspirate was serially centrifuged to result in 12 mL of BMAC	0.051	Arthroscopic rotator cuff repair followed by injection of BMAC of 4 mL in bone-tendon junction, and 8 mL in the bone at the site of the footprint	Arthroscopic rotator cuff repair only	USG and MRI guided tear size assessment
Kim et al[4]	AD-MSC	Auto	Full thickness	The raw lipoaspirates were processed to obtain SVF using enzymatic digestion method using 0.075% collagenase	4.46	Arthroscopic rotator cuff repair followed by injection of AD-MSCs in SVF loaded in 2 mL of fibrin glue scaffold into the tendon-bone approximation and over the repaired tendon	Arthroscopic rotator cuff repair only	VAS, Constant score, UCLA scores, MRI guided tear size assessment
Kim et al[8]	BM-MSC	Auto	Partial thickness	BMAC from BIOMET MarrowStim Mini kit and PRP from BIOMET GPS III kit	1	USG guided injection of 2 mL BMAC with 1 mL of PRP	Rotator cuff exercises taught by experienced physical therapist done daily on their own for 3 mo	VAS, MMT scores, ASES, USG guided tear size assessment
Lamas et al[2]	CE-BM-MSC	Auto	Full thickness	The BM-MSCs isolated from aspirates were expanded during a 2-wk period	20	Open rotator cuff repair with autologous bone marrow in combination with a type I collagen membrane (OrthADAPT)	Open rotator cuff repair with a type I collagen membrane (OrthADAPT™)	VAS, Constant score, MRI guided tear size assessment
Centeno et al[12]	BM-MSC	Auto	Both partial and full thickness	90 mL of bone marrow aspirate was serially centrifuged to a resultant 1-3 mL of buffy coat that is collected. In addition, 60mL of intravenous blood was drawn to isolate PRP and platelet lysate	810	USG guided injection of 1-2 mL of injectate with 60% by volume of BMAC, 20% of PRP, and 20% of platelet lysate	Stretches in all planes along with non-weighted exercises involving scapular stabilizing muscles, triceps, and the rotator cuff muscles for 3 mo	DASH score, SANE, MRI guided tear size assessment
Hurd et al[9]	AD-MSC	Auto	Partial thickness	Transpose RT/Matrase system	11.4	USG guided injection of 5 mL of AD-MSCs	Single injection of 80 mg of methylprednisolone in 2 mL plus 3 mL of 0.25% bupivacaine	Adverse events, ASES, SF-36 score, VAS, MRI guided tear size assessment

AD: Adipose derived; Auto: Autologous; ASES: American shoulder and elbow surgeons; BM: Bone marrow derived; BMAC: Bone marrow aspirate concentrate; CE: Culture expanded; DASH: Disability of the arm, shoulder and hand; MMT: Manual muscle test; PRP: Platelet rich plasma; MRI: Magnetic resonance imaging; MSC: Mesenchymal stem cells; SANE: Single assessment numeric evaluation; SF-36 score: Short form 36 score; SVF: Stromal vascular fraction; UCLA: University of California, Los Angeles; USG: Ultrasonogram; VAS: Visual analog score.