Table 2. A summary of published studies including more than 10 patients after cell therapy in bone defects or bone healing disorders. The medline review showed that cell therapy by bone marrow is not a new technique but has been applied for almost 20 years. According to the scaffold, causative disease, body region and other patient-related factors, most studies demonstrate promising results for bone regeneration by bone marrow cells.

Author	Year	Journal	Bone defect	N patients	Results
Connolly et al.44	1991	CORR	Pseudarthrosis	20	Application of autologous bone marrow (BM) in tibial pseudarthrosis or “non-union”. Post-operative treatment with plaster cast. Additional intramedullary nailing in 10 cases. The authors report that autologous BM application produced the same results as for autologous bone transplantation.
Lokiec et al.63	1996	JBJS-Br	Simple	10 bone cysts	Percutaneous injection of autogenous bone marrow: all the patients became pain-free after two weeks and resumed full activities within six weeks. The cysts were radiologically consolidated and showed remarkable remodeling within four months. Bone healing was achieved 12–48 months after treatment (no complications).
Köse et al.64	1999	Bull Hosp J T Dis	Simple	12 bone cysts	Autologous bone marrow injection in bone cysts: complete healing occurred in 2 patients, whereas 3 cysts showed residual defects. In 6 patient, cysts recurred. Authors concluded that factors such as the size, multi-loculation, and completeness of the filling of the cyst with bone marrow grafting might influence the post-operative outcome.
Hernigou et al.52	2002	CORR	AVN (Hip)	116 (189 hips)	Evaluation of the clinical outcome 5–10 years after core decompression in combination with injection of autologous BM concentrate in the treatment AVN of the femoral head. Very good results in pre-collapse stages (ARCO I-II): 9 out of 145 hips were replaced endoprosthetically. In post-collapse stages, 25 out of 44 hips replaced endoprosthetically. Better results with higher CFU-F and cell numbers.
Rougraff et al.65	2002	JBJS-Am	Unicameral	23 bone cyst	Percutaneous injection of allogeneic demineralized bone matrix augmented with autogenous bone marrow is an effective treatment for unicameral bone cysts.
Chang et al.66	2002	JBJS-Br	Unicameral bone cyst	79	14 patients treated with BM ( 27 injections) vs. 65 patients with steroid application (99 injections). Repeated injections were required in 57% of patients after BM had been used and in 49% after steroid. No complications. No advantage could be shown for the use of autogenous injection of BM compared with injection of steroid in the management of unicameral bone cysts.
Price et al.67	2003	Spine	Spinal fusion	77	Retrospective study with 3 different bone grafting techniques: autologous iliac crest bone graft (ICBG) vs. freeze-dried corticocancellous allograft vs. composite graft of autologous bone marrow (BM) and demineralized bone matrix. Segmental instrumentation with dual-rod fixation was used in 77 patients. No BM aspiration-associated morbidity. Fusion rates were comparable for ICBG and BM group.
Docquier et al.68	2003	J Pediatr Orthop	Simple bone cyst	17	Percutaneous aspiration and injection of BM. FU: 33.9 months. Slow regression of the cyst and progressive healing: 13 cases (76%). No response: 2 cases (12%), recurrence: 2 cases (12%).
Gangji et al59	2004	JBJS-Am	AVN (hip)	13 (18 hips)	Necrosis of the femoral head in ARCO stages I-II. Core decompression (vs. core decompression + BM aspirate (10 patients). Within 24 months, significant reduction in pain, functional improvement and lower AVN progression rate after cell therapy. No transplantation-related complications.
Hernigou et al.33	2005	JBJS-Am	Pseudarthrosis /non-unions (atrophic, tibia)	60	Injection of 20 cm3 BM concentrate: 612±34 progenitor cells/cm3 in the aspirate compared to 2579±1121 progenitor cells/cm3 after density gradient centrifugation: healing in 53 cases. Positive correlation between callus regeneration and the number of CFUs.
Kanellopoulos69	2005	J Pediatric Orthop	Active unicameral bone cyst	19	BM injection in bone cysts. All patients were asymptomatic at the latest follow up. Two patients required a second intervention to achieve complete cyst healing. Radiographic outcome was improved in all patients according to the Neer classification at the latest FU. There were no significant complications related to the procedure, nor did any fracture occur after initiation of the above regimen.
Neen et al.51	2006	Spine	Spinal fusions	50	Therapy using HA-collagen I composite incubated with autologous BM aspirate (incubation time: 20 min) vs. autologous bone transplantation The same posterolateral lumbar fusion rates for both groups, similar functional results for both groups. Autologous bone transplantations raised the fusion rate in “interbody fusions”, but donor-site morbidity in 14% of the cases.
Yan et al.70	2006	Chin J Traumatol	AVN (hip)	28 (44 hips)	Percutaneous multiple hole decompression combined with autologous BMCs. The earlier the stage, the better the result. A randomized prospective study needed in the future to compare with routine core decompression.
Dallari et al.45	2007	JBJS-Am	Proximal	33 tibia osteotomies	Prospective, randomized study with 2 therapy groups: lyophilized bone chips + PRP (A, 11 patients) vs. lyophilized bone chips + PRP + bone marrow (B, 12patients). Control group: lyophilized bone chips only. CT-controlled biopsies six weeks post-OP showed increased callus formation in A and B compared to the control group. Improved bone healing in A and B within one year.
Deng et al.71	2007	Chin J Regen Reconstr Surg	Bone cyst	13	Transplantation of the autologous bone marrow combined with the allograft bone. Complete healing within 3.5–8 months (Ø 5.2 months). No recurrence, no pathological fracture occurred. Complete recovery of function.
Cho et al.72	2007	JBJS-Br	Bone cysts	28 (58)	30 patients treated by steroid injection vs. 28 individuals by bone marrow grafting. Overall success rates: 86.7% vs. 92.0%, respectively (P>0.05). Initial success rate: 23.3% in the steroid group vs. 52.0% in the BM group. Mean number of procedures: 2.19 (1 to 5) vs. 1.57 (1 to 3) (P<0.05). Average healing interval: 12.5 months (4–32) P =14.3 months (7–36) (P>0.05). Rate of recurrence after initial procedure: 41.7% vs. 13.3% (P<0.05). Although the overall rates of success of both methods were similar, the steroid group showed higher recurrences after a single procedure and required more injections to achieve healing.
Wright et al.49	2008	JBJS-Am	Bone cysts	77	Randomized, prospective study. Two therapy groups: injection of autologous BM (A) vs. injection of methylprednisolone (B). Healing rate within two years: 23% (A) vs. 42% (B). No significant difference in the functional outcome.
Park et al.47	2008	Foot Ankle	Bone cysts	20 (23 cysts)	Therapy of unicameral bone cysts of the calcaneus. Two therapy groups: open surgery application of avital allogenic donor bone + autologous BM (A) vs. injection of demineralized bone powder + autologous BM (B). Healing rate within 49.4 months: A: 9 out of 13 cysts vs. B: 5 out of 10 cysts. No infections.
Gan et al.50	2008	Biomaterials	Spinal fusions	41	Application of TCP incubated with BM concentrate (duration circa 2 h). Concentration factor (CFUs-ALP: 4.3). Drop in MSCs with increasing age, but no dependency on gender. After 34.5 months, spinal fusion in 95.1% of the cases.
Zamzam et al.48	2008	Int Orthop	Solitary bone cysts	28	A minimum one-off percutaneous injection of autologous BM. No complications. Within 34.7±6.87 months, bone healing in 82% of the cases.
Jäger et al.73	2009	CSCRT	Bone defects	10	Significant bone regeneration through bone marrow concentrate (BMAC) in combination with autologous cancellous bone.
Hendrich et al.29	2009	Orthop Rev	Bone defects, AVN	101	Proof of the low complication risk of autologous BMAC in 101 applications.
Giannini et al.43	2009	CORR	Osteochondral lesions (talus)	48	Functional improvements after arthroscopy-assisted application of autologous BM aspirate in osteochondral defects in the talus.
Sir et al.74	2009	Vnitr Lek	Fracture-related bone defects, pseudarthrosis	11	Local and one-step injection of MSCs from human BM. Results pending.
Kitoh et al.46	2009	J Pediatr Orthop	Tibial vs.femoral lengthening osteotomies	28 (51 osteotomies)	Retrospective study. Application of ex vivo cultivated MSCs together with PRP Control group: 60 patients without MSC/PRP. No stimulation of bone healing by MSC/PRP. Worse results for the tibia.
Hernigou et al.56	2009	Indian J Orthop	AVN (hip)	342 (534 hips)	Autologous cell therapy in ARCO stages I–II in combination with a core decompression. After 8–18 years, 94 endoprosthetic hip replacements. Predictor for a therapy success was a high number of progenitor cells.
Wang et al.75	2009	Arch Orthop Trauma Surg	AVN (hip)	45 (59 hips)	BMAC injection in AVN of the femoral head (ARCO stage I–III).Clinically successful in 79.7%. Hip replacement within FU in 11.9% of the hips. Radiologically, 14 of the 59 hips exhibited femoral head collapse or narrowing of the joint space. Overall failure rate: 23.7%. The concentration factor of mononuclear cells from BM vs. BMAC was about 3.
Miller et al.76	2010	Int Orthop	Non-union or segmental defect	13	Bone marrow cells harvested by a reamer-irrigator-aspirator (RIA) were treated by dexamethason and transplanted into segmental bone defects. Promising results were achieved using this technique; and given the complexity of these cases, the observed success is of great value and warrants controlled study into both standardization of the procedure and concentration of the grafting material.
Yamasaki et al.77	2010	JBJS-Br	AVN (hip)	22 (30 hips)	Transplantation of bone-marrow-derived mononuclear cells (BMMNCs) combined with hydroxypapatite (HA) vs. HA only in AVN of the femoral head. Reduction of the osteonecrotic lesion was observed subsequent to hypertrophy of the bone in the transition zone in the BM group. In 3 patients of the BMMNC group, progression to extensive collapse occurred. Control group showed bone hypertrophy, but severe collapse of the femoral head occurred in 6 of 8 hips.