Stem-cell therapy for ovariectomy-induced osteoporosis in rats: a comparison of three treatment modalities

Figures & data

Table 1 Structural indices of distal femur in the four groups analyzed by high-resolution peripheral quantitative computed tomography

Parameter	Group 1 (control)	Group 2 (MSCs)	Group 3 (osteoblasts)	Group 4 (exosomes)
TV, mm^3 (voxels)	42.178±4.727	38.894±5.528	31.615±1.331	42.836±4.563
BV, mm^3 (voxels)	3.933±1.540	3.954±0.967	5.959±1.953	4.274±0.930
BV/TV, % (voxels)	0.091±0.027	0.102±0.021	0.191±0.071	0.099±0.015
Trabecular number, 1/mm(voxels)	0.839±0.268	0.850±0.315	2.813±2.324	0.869±0.104
Trabecular thickness, 1/mm (voxels)	0.081±0.002	0.082±0.004	0.064±0.001	0.076±0.004
Connectivity density (normed by TV), 1/mm^3 (voxels)	27.765±12.122	32.061±7.396	167.767±81.358	33.741±5.493
Trabecular separation (marrow thickness), mm (voxels)	1.348±0.441	1.364±0.453	0.552±0.327	1.245±0.178
TV, mm^3 (Tri)	41.753±4.696	38.483±5.499	31.234±1.315	42.401±4.550
BV, mm^3 (Tri)	3.933±1.540	3.892±0.962	5.810±1.972	4.212±0.928
BS (Tri)	107.696±27.559	120.488±30.732	228.553±69.641	137.280±27.154
BS/BV (Tri)	32.061±0.886	30.951±2.123	39.622±1.512	32.750±1.582
Trabecular number, 1/mm (Tri)	1.440±0.396	1.562±0.297	3.695±1.300	1.610±0.184
Trabecular thickness, 1/mm (Tri)	0.062±0.002	0.065±0.004	0.071±0.002	0.061±0.003
Trabecular spacing	0.671±0.215	0.590±0.119	0.240±0.087	0.566±0.079

Note: Tri, based on Triangularization of surface. Data shown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; MSCs, mesenchymal stem cells; BS, bone surface.

Figure 1 Distal femur analyzed by high-resolution peripheral quantitative computed tomography compariing control (A) and treated groups of mesenchymal stem cells (B), osteoblasts (C), and exosomes (D).

Figure 2 Sagittal sections of distal femur analyzed by high-resolution peripheral quantitative computed tomography compairing control (A) and treated groups of mesenchymal stem cells (B), osteoblasts (C), and exosomes (D).

Table 2 Comparison between control versus MSCs for distal femur

Parameter	Group 1 (control)	Group 2 (MSCs)	P-value
TV, mm^3 (voxels)	42.178±4.727	38.894±5.528	0.093
BV,  mm^3 (voxels)	3.933±1.540	3.954±0.967	0.9
BV/TV, % (voxels)	0.091±0.027	0.102±0.021	0.06
Trabecular number, 1/mm (voxels)	0.839±0.268	0.850±0.315	0.9
Trabecular thickness, 1/mm (voxels)	0.081±0.002	0.082±0.004	0.5
Connectivity density, normed by TV, 1/mm^3 (voxels)	27.765±12.122	32.061±7.396	0.09
Trabecular separation = marrow thickness, mm (voxels)	1.348±0.441	1.364±0.453	0.53
TV, Tmm^3 (TRI)	41.753±4.696	38.483±5.499	0.09
BV, TV mm^3 (TRI)	3.933±1.540	3.892±0.962	0.89
TRI- BS	107.696±27.559	120.488±30.732	0.22
TRI- BS/BV	32.061±0.886	30.951±2.123	0.13
Trabecular number, 1/mm (TRI)	1.440±0.396	1.562±0.297	0.22
Trabecular thickness, 1/mm (TRI)	0.062±0.002	0.065±0.004	0.04
Trabecular spacing	0.671±0.215	0.590±0.119	0.05

Note: Tri, based on Triangularization of surface. Data shown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; BS, bone surface.

Table 3 Comparison between control versus osteoblasts for distal femur

Parameter	Group 1 (control)	Group 3 (osteoblasts)	P-value
TV, mm^3 (voxels)	42.178±4.727	31.615±1.331
BV, mm^3 (voxels)	3.933±1.540	5.959±1.953	0.009
BV/TV, % (voxels)	0.091±0.027	0.191±0.071	0.001
Trabecular number, 1/mm (voxels)	0.839±0.268	2.813±2.324	0.025
Trabecular thickness, 1/mm (voxels)	0.081±0.002	0.064±0.001	0.01
Connectivity density, normed by TV, 1/mm^3 (voxels)	27.765±12.122	167.767±81.358	0.0004
Trabecular separation = marrow thickness, mm (voxels)	1.348±0.441	0.552±0.327	0.0001
TV, Tmm^3 (TRI)	41.753±4.696	31.234±1.315	0.001
BV, mm^3 (TRI)	3.933±1.540	5.810±1.972	0.01
TRI- BS	107.696±27.559	228.553±69.641	0.0004
TRI- BS/BV	32.061±0.886	39.622±1.512	0.0001
Trabecular number, 1/mm (TRI)	1.440±0.396	3.695±1.300	0.0004
Trabecular thickness, 1/mm (TRI)	0.062±0.002	0.071±0.002	0.001
Trabecular spacing	0.671±0.215	0.240±0.087	0.0001

Note: Tri, based on Triangularization of surface. Data shown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; MSCs, mesenchymal stem cells; BS, bone surface.

Table 4 Comparison between control versus exosomes for distal femur

Parameter	Group 1 (control)	Group 4 (exosomes)	P-value
TV, mm^3 (voxels)	42.178±4.727	42.836±4.563	0.2
BV, mm^3 (voxels)	3.933±1.540	4.274±0.930	0.2
BV/TV, % (voxels)	0.091±0.027	0.099±0.015	0.06
Trabecular number, 1/mm (voxels)	0.839±0.268	0.869±0.104	0.3
Trabecular thickness, 1/mm (voxels)	0.081±0.002	0.076±0.004	0.02
Connectivity density, normed by TV, 1/mm^3 (voxels)	27.765±12.122	33.741±5.493	0.007
Trabecular separation = marrow thickness, mm (voxels)	1.348±0.441	1.245±0.178	0.3
TV, Tmm^3 (TRI)	41.753±4.696	42.401±4.550	0.4
BV, mm^3 (TRI)	3.933±1.540	4.212±0.928	0.3
TRI- BS	107.696±27.559	137.280±27.154	0.06
TRI- BS/BV	32.061±0.886	32.750±1.582	0.3
Trabecular number, 1/mm (TRI)	1.440±0.396	1.610±0.184	0.01
Trabecular thickness, 1/mm (TRI)	0.062±0.002	0.061±0.003	0.2
Trabecular spacing	0.671±0.215	0.566±0.079	0.002

Note: Tri, based on Triangularization of surface. Data shown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; BS, bone surface.

Table 7 Comparison between control versus osteoblasts for spinal indices

Parameter	Group 1 (control)	Group 3 (osteoblasts)	P-value
TV, mm^3 (voxels)	21.854±5.980	15.592±5.397	0.001
BV, mm^3 (voxels)	3.238±0.534	4.677±0.611	0.001
BV/TV, % (voxels)	0.152±0.023	0.315±0.067	0.001
Trabecular number, 1/mm (voxels)	2.122±0.549	4.100±0.307	0.001
Trabecular thickness, 1/mm (voxels)	0.072±0.002	0.075±0.006	0.01
Connectivity density, normed by TV, 1/mm^3 (voxels)	38.553±3.724	87.915±12.768	0.001
Trabecular separation = marrow thickness, mm (voxels)	0.502±0.142	0.235±0.20	0.002
TV, Tmm^3 (TRI)	21.539±5.911	15.354±5.314	0.001
BV, mm^3 (TRI)	3.202±0.517	4.717±0.593	0.001
TRI- BS	108.232±23.101	139.988±35.988	0.001
TRI- BS/BV	33.622±1.696	29.454±4.809	0.022
Trabecular number, 1/mm (TRI)	2.556±0.318	4.644±0.378	0.001
Trabecular thickness, 1/mm (TRI)	0.063±0.003	0.069±0.010	0.002
Trabecular spacing	0.336±0.048	0.147±0.029	0.001

Note: Tri, based on Triangularization of surface. Datashown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; BS, bone surface.

Figure 3 Lumbar fourth vertebral body analyzed by high-resolution peripheral quantitative computed tomography compariing control (A) and treated groups of mesenchymal stem cells (B), osteoblasts (C), and exosomes (D).

Table 5 Structural indices of spine in the four groups as analyzed by HRpQCT

Parameter	Group 1 (control)	Group 2 (MSCs)	Group 3 (osteoblasts)	Group 4 (exosomes)
TV, mm^3 (voxels)	21.854±5.980	19.173±2.450	15.592±5.397	23.004±6.644
BV, mm^3 (voxels)	3.238±0.534	3.325±0.549	4.677±0.611	4.549±1.787
BV/TV, % (voxels)	0.152±0.023	0.173±0.007	0.315±0.067	0.194±0.033
Trabecular number, 1/mm (voxels)	2.122±0.549	2.180±0.341	4.100±0.307	2.648±0.100
Trabecular thickness, 1/mm (voxels)	0.072±0.002	0.077±0.006	0.075±0.006	0.075±0.006
Connectivity density, normed by TV, 1/mm^3 (voxels)	38.553±3.724	37.310±3.904	87.915±12.768	46.901±4.202
Trabecular separation = marrow thickness, mm (voxels)	0.502±0.142	0.472±0.093	0.235±0.20	0.368±0.012
TV, Tmm^3 (TRI)	21.539±5.911	18.865±2.435	15.354±5.314	22.678±6.591
BV, mm^3 (TRI)	3.202±0.517	3.301±0.554	4.717±0.593	4.540±1.811
TRI- BS	108.232±23.101	100.067±19.317	139.988±35.988	137.803±44.209
TRI- BS/BV	33.622±1.696	30.263±1.662	29.454±4.809	31.208±3.336
Trabecular number, 1/mm (TRI)	2.556±0.318	2.643±0.237	4.644±0.378	3.018±0.279
Trabecular thickness, 1/mm (TRI)	0.063±0.003	0.066±0.004	0.069±0.010	0.065±0.007
Trabecular spacing	0.336±0.048	0.314±0.032	0.147±0.029	0.269±0.036

Note: Tri, based on Triangularization of surface. Data shown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; MSCs, mesenchymal stem cells; BS, bone surface; HRpQCT, high resolution peripheral quantitative computed tomography.

Table 6 Comparison between control versus MSCs for spinal indices

	Group 1 (control)	Group 2 (MSCs)	P-value
TV, mm^3 (voxels)	21.854±5.980	19.173±2.450	0.007
BV, mm^3 (voxels)	3.238±0.534	3.325±0.549	0.6
BV/TV, % (voxels)	0.152±0.023	0.173±0.007	0.001
Trabecular number, 1/mm (voxels)	2.122±0.549	2.180±0.341	0.603
Trabecular thickness, 1/mm (voxels)	0.072±0.002	0.077±0.006	0.027
Connectivity density, normed by TV, 1/mm^3 (voxels)	38.553±3.724	37.310±3.904	0.340
Trabecular separation = marrow thickness, mm (voxels)	0.502±0.142	0.472±0.093	0.334
TV, Tmm^3 (TRI)	21.539±5.911	18.865±2.435	0.007
BV, mm^3 (TRI)	3.202±0.517	3.301±0.554	0.3
TRI- BS	108.232±23.101	100.067±19.317	0.2
TRI- BS/BV	33.622±1.696	30.263±1.662	0.002
Trabecular number, 1/mm (TRI)	2.556±0.318	2.643±0.237	0.4
Trabecular thickness, 1/mm (TRI)	0.063±0.003	0.066±0.004	0.041
Trabecular spacing	0.336±0.048	0.314±0.032	0.057

Note: Tri, based on Triangularization of surface.

Abbreviations: TV, total volume; BV, bone volume; BS, bone surface.

Table 8 Comparison between control versus exosomes for spinal indices

Parameter	Group 1 (control)	Group 4 (exosomes)	P-value
TV, mm^3 (voxels)	21.854±5.980	23.004±6.644	0.590
BV, mm^3 (voxels)	3.238±0.534	4.549±1.787	0.04
BV/TV, % (voxels)	0.152±0.023	0.194±0.033	0.003
Trabecular number, 1/mm (voxels)	2.122±0.549	2.648±0.100	0.001
Trabecular thickness, 1/mm (voxels)	0.072±0.002	0.075±0.006	0.001
Connectivity density, normed by TV, 1/mm^3 (voxels)	38.553±3.724	46.901±4.202	0.0002
Trabecular separation = marrow thickness, mm (voxels)	0.502±0.142	0.368±0.012	0.001
TV, Tmm^3 (TRI)	21.539±5.911	22.678±6.591	0.598
BV, mm^3 (TRI)	3.202±0.517	4.540±1.811	0.044
TRI- BS	108.232±23.101	137.803±44.209	0.06
TRI- BS/BV	33.622±1.696	31.208±3.336	0.048
Trabecular number, 1/mm (TRI)	2.556±0.318	3.018±0.279	0.006
Trabecular thickness, 1/mm (TRI)	0.063±0.003	0.065±0.007	0.389
Trabecular spacing	0.336±0.048	0.269±0.036	0.002

Note: Tri, based on Triangularization of surface. Data shown as mean ± SD.

Abbreviations: TV, total volume; BV, bone volume; BS, bone surface.