Table 1.
Author | Year | Ref | FU (y) | Site | Mode | Product | Cell density | Volume and carrier | n | Control(s) | n | Efficacy | Safety | Type |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Yoshikawa | 2010 | [36] | 2 | ID | Autologous | BM-MSC | Unclear | 0.54mL collagen sponge | 2 | - | - | ✔ | ✔ | Mesenchymal stromal cells |
Orozco | 2011 | [37] | 1 | ID | Autologous | BM-MSC | 10×106/mL | 0.5-1.5mL saline | 10 | - | - | ✔ | ✔ | |
Centeno | 2017 | [38,39] | 6 | ID* | Autologous | BM-MSC | 23×106/disc | 1-3mL 10-20% PL/PBS | 33 | - | - | ✔ | ✔ | |
Noriega | 2021 | [40], [41], [42] | 3.5 | ID | Allogenic | BM-MSC | 12.5×106/mL | 2mL saline | Unclear | Muscle anesthetic | Unclear | ✔ | ✔ | |
Papadimitriou | 2021 | [43,44] | 2 | ID | Autologous | BM-MSC | 1×106/mL | 1mL 20% serum/F12 | 10 | - | - | ✔ | ✔ | |
Amirdelfan | 2021 | [45,46] | 3 | ID | Allogenic | MPC | High: 18×106/disc Low: 6×106/disc |
2mL HA | 60 | HA (Vehicle) Saline (Placebo) |
20 20 |
✔ | ✔ | |
Jung | 2013 | [47] | <0.5 | IV | Autologous | AD-MSC | Unspecified | Unspecified | 3 | - | - | ✘ | ✔ | |
Piccirilli | 2017 | [48] | 1 | ID | Autologous | AD-MSC | Unspecified | 1mL solution | 2 | - | - | ✘ | ✔ | |
Kumar | 2017 | [49] | 1 | ID | Autologous | AD-MSC | High: 20×106/disc Low: 10×106/disc |
2mL HA | 5 5 |
- | - | ✔ | ✔ | |
Bates | 2022 | [50] | 1 | ID | Autologous | AD-MSC | 10×106/disc | 1mL saline | 9 | - | - | ✔ | ✔ | |
Zhang | 2022 | [51] | 2 | ID | Autologous | AD-MSC | High: 20×106/disc Mid: 10×106/disc Low: 5×106/disc |
2mL HA | 25 25 25 |
Saline (Placebo) | 25 | ✘ | ✘ | |
Pang | 2014 | [52] | 2 | ID | Allogenic | UC-MSC | 10×106/mL | 1mL solution | 2 | - | - | ✔ | ✔ | |
Meisel | 2006 | [53], [54], [55] | 2 | ID | Autologous | IVD-C | Unspecified | Unspecified | 12 | Discectomy-only | 16 | ✔ | ✘ | Chondrogenic cells |
Mochida | 2015 | [56] | 3 | ID | Autologous | NPC | ∼1.5×106 | 0.7 mL saline | 9 | - | - | ✔ | ✔ | |
Tschugg | 2017 | [57,58] | <0.5 | ID | Autologous | IVD-C | Unclear | PEG + serum + media | 12 | Discectomy + HA (Vehicle) |
12 | ✘ | ✔ | |
Schwan | 2017 | [59] | n.a. | ID | Autologous | IVD-C | Unspecified | Saline OR `polymerizing-scaffold` | 10 | Discectomy-only | 10 | ✘ | ✔ | |
Beall | 2020 | [60] | 1 | ID | Allogenic | NPC | Unclear | 1.75mL NP tissue | 16 | Saline (Placebo) Conservative care |
4 4 |
✔ | ✔ | |
Hunter | 2022 | [61,62] | 1 | ID | Allogenic | NPC | Unclear | 1.75mL NP tissue | 140 | Saline (Placebo) Conservative care |
39 39 |
✔ | ✔ | |
Foley | 2022 | [63] | 1.5 | ID | Allogenic | NPC | High: 9×106/disc Low: 3×106/disc |
1mL HA | 20 20 |
Saline (Placebo) HA (Vehicle) |
10 10 |
✔ | ✔ | |
Xuan | 2022 | [64] | 6 | ID | Autologous | IVD-C | 4-7×106/disc | 1-3mL saline | 18 | Discectomy-only | 22 | ✔ | ✔ | |
Coric | 2013 | [65] | 1 | ID | Allogenic | AC | 10×106/mL | 1-2mL fibrin | 15 | - | - | ✔ | ✔ | |
Comella | 2017 | [66] | 1 | ID | Autologous | SVF | 30-60×106/1-3 disc | 1mL PRP | 15 | - | - | ✔ | ✔ | Mixture of cells |
Pettine | 2017 | [67], [68], [69] | 3 | ID | Autologous | BMC | 130×106/mL | 2-3mL solution | 26 | - | - | ✔ | ✔ | |
Wolff | 2020 | [70] | 1 | ID | Autologous | BMC | Unspecified | 3mL solution | 33 | - | - | ✔ | ✔ | |
Ramos | 2020 | [71] | 1 | ID | Autologous | BMC | Unspecified | Unspecified mL PRP | 1 | - | - | ✘ | ✔ | |
El-Kadiry | 2021 | [72] | 1 | ID | Autologous | BMC | Unspecified | 1-6mL solution | 13 | - | - | ✔ | ✔ | |
Jerome | 2021 | [73] | <0.5 | ID | Autologous | BMC | Unspecified | Unspecified | 3 | - | - | ✘ | ✔ | |
Xu | 2021 | [74] | 2 | ID | Autologous | BMA | Unspecified | ∼1.25mL gelatin sponges | 15 | Discectomy-only Discectomy + AF suture |
15 15 |
✔ | ✔ | |
Subach | 2011 | [75] | 1 | ID | Autologous | BMA + AT + Plasma | Unspecified | 3mL solution | 1 | - | - | ✘ | ✔ | |
Haufe | 2005 | [76] | 1 | ID | Autologous | HSC | Unspecified | Unspecified | 10 | - | - | ✔ | ✘ |
Efficacy and Safety columns represent whether outcomes are reported presenting overall improvements in pain, disability, quality of life, or image modalities or the presence of (serious) adverse events following cell therapy respectively; ✔: reported, ✘: not reported. * MSC was transplanted intradiscally, treatment was complemented with epidural injection of PL. Abbreviations: AC – Articular cartilage derived cells, AD-MSC- Adipose derived mesenchymal cells, AF – Annulus fibrosis, AT – Adipose tissue, BMA – Bone marrow aspirate, BMC – Bone marrow concentrate, BM-MSC - Bone marrow derived mesenchymal stromal cells, FU – (maximal) Follow up, HA – Hyaluronic acid, HSC – Hematopoietic stem cells, ID – Intradiscal, IV – Intravenous, IVD-C – Intervertebral disc derived cells, MPC - Mesenchymal precursor cells, N.A. – Not applicable, NP – Nucleus pulposus, NPC – Nucleus pulposus cells, PBS – Phosphate buffered saline, PEG - Polyethylene glycol, PL – Platelet lysate, PRP – Platelet rich plasma, REF – Reference, and SVF – Stromal vascular fraction, and UC-MSC – Umbilical cord mesenchymal stromal cells.